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The prevalence of age-related macular degeneration in India is lower than in America and Europe at 0.61 to 1.9%. Studies have shown that dietary patterns and consumption of certain food groups can influence the prevalence of agerelated macular degeneration (ARMD) in a given population. This study's goal was to evaluate the impact of dietary fat and food consumption patterns in Indians with ARMD and compare it to age-matched healthy individuals. 90 patients from a Mumbai ophthalmology outpatient clinic who were above 50 years were recruited to participate in the research. The participants were divided into groups of those with and without ARMD based on the fundus assessment. For each of the meals, a food frequency questionnaire was utilized to record the common foods that all of the individuals ate. They were asked to remember the foods they had just ingested. Based on consumption patterns, some were grouped as vegetarians who had only plant-based foods and others as non-vegetarians who consumed meat, fish and eggs. Using a conversion table created for Indian meals, the intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids was quantified. The information was then analyzed between those with and without ARMD. 45/90 people were in the control group, and among the 45 cases. The amount of MUFA consumed was 44.29±26.00 and 40.53±17.18 and PUFA consumed was 35.57±26.34 and 43.61±27.27 by the cases and controls discretely. With regard to dietary fats, there was no statistically significant difference between them p=0.05. Further, the food types consumption was analysed and it showed that 13% of the cases were vegetarians whereas 47% of the controls were vegetarians. 12% of the servings consumed in the cases had meat whereas only 3% of the servings contained meat among the controls. The control group consumed 1.7% servings of fish whereas the cases consumed 0.59%. The present study results show that Indians consume foods rich in PUFA which could lower the risk of ARMD. The results further indicate that subjects who consumed more vegetarian foods and were lower on meat were at a reduced risk to develop ARMD. [ABSTRACT FROM AUTHOR]

This case study aims to evaluate the regression of the vascular network in a patient with age-related macular degeneration (AMD) following a single injection of faricimab, utilizing optical coherence tomography angiography (OCTA) for detailed assessment. An elderly patient diagnosed with neovascular AMD received a single injection of faricimab, with pre and post-treatment OCTA imaging performed to assess changes in the choroidal neovascular membrane (CNVm) and surrounding retinal structures. OCTA revealed significant regression of the vascular network following the single injection of faricimab, demonstrating a marked reduction in blood flow within the CNV, which corresponded with structural and anatomical improvements in the retina. This case highlights the potential of faricimab to induce rapid regression of CNVm in AMD after a single injection, as observed through OCTA. Furthermore, while current monitoring primarily relies on OCT B-scan structural assessments, the flow dynamics captured by OCTA may play a crucial role in future treatment monitoring and therapeutic strategies for managing neovascular AMD., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Alsatrawi et al.)

Purpose: To evaluate the clinical characteristics associated with chronic pachychoroid neovasculopathy (PNV) accompanying recalcitrant intraretinal cysts., Methods: This is a retrospective, single-center, case-series study involving 20 eyes of 18 patients with PNV who did not respond to bevacizumab or ranibizumab and had to switch to aflibercept. Optical coherence tomography images were assessed before and after switching of intravitreal injection drug., Results: The intraretinal cysts involved the outer nuclear layer and inner nuclear layer in 15 patients (75.0%), and involved only the inner nuclear layer in five patients (25.0%). All participants showed retinal pigment epithelium atrophy and outer retinal layer defect including external limiting membrane defect co-localized to the intraretinal cystic lesion. With the initial injection, bevacizumab and ranibizumab injections did not show a significant decrease in choroidal thickness (CT). Twenty (100.0%) patients showed poor response of intraretinal cyst response (IRCR). After a switch to aflibercept, IRCR was good in 17 (85.0%) patients and poor in three (15.0%) patients. Reduction of CT was great in aflibercept injections (from 229.0 μm to 204.0 μm, median, p < 0.001). Best-corrected visual acuity did not show significant improvement before or after switching drugs., Conclusion: Intravitreal aflibercept injections were more effective in the reduction of CT and IRCR than bevacizumab and ranibizumab injections. The primary source of the intraretinal cyst fluid could be from the choroid., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Won Ki Lee declare(s) personal fees from Bayer. Won Ki Lee has served on advisory boards for Bayer and has received consultancy fee from this company. He has received payments for lectures from Bayer. Won Ki Lee declare(s) personal fees from Novartis. Won Ki Lee has served on advisory boards for Novartis and has received consultancy fee from this company. He has received payments for lectures from Novartis. Won Ki Lee declare(s) personal fees from Roche. Won Ki Lee has served on advisory boards for Roche and has received consultancy fee from this company. He has received payments for lectures from Roche. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Choi et al.)

Age-related macular degeneration (ARMD) is a degenerative ocular disease that is the most important cause of irreversible vision loss in old-aged people in developed countries. Around fifty percent of vision impairments in developed countries are due to ARMD. It is a multifaceted disease that is associated with both genetic and environmental risk factors. The most important treatments option for ARMD includes laser photocoagulation, photodynamic therapy (PDT), Anti-VEGF Injections, and combination therapies. In this review, we also propose that topical ocular drug delivery with nanocarriers has more attention for the treatment of ARMD. The nanocarriers were specially designed for enhanced corneal residential time, prolonged drug release and action, and minimizing the frequency of administrations. Different types of nanocarriers were developed for the topical ocular delivery system, such as nanomicelles, nanoemulsions, nanosuspensions, liposomes, and polymeric nanoparticles. These topical ocular nanocarriers were administered topically, and they can fix the hydrophobic substances, increase solubility and improve the bioavailability of an administered drug. Hence the topical ocular delivery systems with nanocarriers provide a safe and effective therapeutic strategy and promising tool for the treatment of posterior segment ocular diseases ARMD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Conventional, allopathic treatments for age-related macular degeneration (ARMD), the most common cause of irreversible blindness in people over 65 years of age, are fraught with limitations and toxic side effects. Homeopathy, by contrast, offers a safe and effective treatment for this condition. The following three cases exemplify the unique way that homeopathy treats the individual with ARMD rather than just the condition itself; each patient required a completely different homeopathic medicine according to the Law of Similars. [ABSTRACT FROM AUTHOR]

Background: Age-related macular degeneration (ARMD), a progressive retinal disease, is responsible for an impaired central vision in about 180 million people worldwide. Current options for ARMD prevention and treatment are limited due to an incomplete understanding of disease etiopathogenesis. We aimed to test the hypothesis that the single nucleotide polymorphism rs5888 of SCARB1 gene reflecting lipid and antioxidant micronutrient metabolism pathways is associated with ARMD susceptibility and to evaluate if there is any relation between SCARB1 rs5888 and the macular lesion area. Materials and methods: The prospective case-control study included patients with ARMD (n = 215) and the reference group (n = 238) drawn from a random sample of the Lithuanian population (n = 1436). The genotyping test of SCARB1 rs5888 was carried out using the real-time polymerase chain reaction method. Results: Regression analysis adjusted by gender and age demonstrated that SCARB1 rs5888 TT genotype significantly decreased the odds for ARMD development (OR: 0.61, 95%; CI: 0.380-0.981, p = 0.04). A smoking habit and leading an outdoor life are associated with larger macular lesion areas in ARMD patients (0.54 (0.00-39.06) vs. 3.09 (0.02-19.30) and 0.27 (0.00-34.57) vs. 0.75 (0.00-39.06), respectively). In late stage ARMD subjects with CT genotype, the macular lesion area was larger than in TT carriers (7.64 (0.49-39.06) mm² vs. 5.02 (0.03-37.06) mm², p = 0.006). Conclusions: SCARB1 rs5888 and environmental oxidative stress have a prominent role in ARMD susceptibility, early ARMD progression to advanced stage disease and even in the outcome of the disease--an area of macular lesion. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (ARMD) is the leading cause of vision loss in developed countries. Hallmarks of the disease are well known; indeed, this pathology is characterized by lipofuscin accumulation, is principally composed of lipid-containing residues of lysosomal digestion. The N-retinyl-N-retinylidene ethanolamine (A2E) retinoid which is thought to be a cytotoxic component for RPE is the best-characterized component of lipofuscin so far. Even if no direct correlation between A2E spatial distribution and lipofuscin fluorescence has been established in aged human RPE, modified forms or metabolites of A2E could be involved in ARMD pathology. Mitogen-activated protein kinase (MAPK) pathways have been involved in many pathologies, but not in ARMD. Therefore, we wanted to analyze the effects of A2E on MAPKs in polarized ARPE19 and isolated mouse RPE cells. We showed that long-term exposure of polarized ARPE19 cells to low A2E dose induces a strong decrease of the extracellular signal-regulated kinases' (ERK1/2) activity. In addition, we showed that A2E, via ERK1/2 decrease, induces a significant decrease of the retinal pigment epithelium-specific protein 65 kDa (RPE65) expression in ARPE19 cells and isolated mouse RPE. In the meantime, we showed that the decrease of ERK1/2 activity mediates an increase of basic fibroblast growth factor (bFGF) mRNA expression and secretion that induces an increase in phagocytosis via a paracrine effect. We suggest that the accumulation of deposits coming from outer segments (OS) could be explained by both an increase of bFGF-induced phagocytosis and by the decrease of clearance by A2E. The bFGF angiogenic protein may therefore be an attractive target to treat ARMD. [ABSTRACT FROM AUTHOR]

Smoking is a widespread and pervasive habit, impacting health across various care settings, including acute care, subacute care, home-based care, and long-term care. Smoking is a serious global public health concern that has been related to many chronic diseases. However, the effect of smoking on eye disorders has been less studied. Cigarette smoke contains a complex mixture of harmful constituents, including nicotine and toxic chemicals, which permeate the bloodstream, affecting ocular tissues. The oxidative stress and inflammation induced by smoking are central to its detrimental effects on ocular health. Age-related macular degeneration (AMD), a leading cause of vision loss, exhibits a strong association with smoking. Research consistently demonstrates that smokers face a heightened risk of both early and advanced AMD. Cataracts, another prevalent ocular condition, develop earlier and progress more rapidly in smokers. The oxidative stress on the lens and reduced antioxidants among smokers contribute to the increased severity of cataracts. Moreover, the health of the eyes may be compromised by smoking-related chemicals that reduce blood flow and/or hasten thrombus formation in ocular capillaries thus increasing the chance of acquiring glaucoma, cataracts, AMD, and Graves' eye disease. Beyond individual health concerns, the societal implications of smoking on ocular health are substantial, including increased healthcare costs and diminished quality of life for affected individuals. Understanding the underlying mechanisms can provide insights into potential therapeutic interventions for preventing and managing smoking-related ocular damage. Given the global prevalence of smoking, raising awareness about the ocular risks associated with smoking is crucial for promoting eye health. The review underscores the urgent need for comprehensive anti-smoking initiatives and smoking cessation programs to alleviate the burden of ocular diseases associated with smoking., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Kulkarni et al.)

Powerful blue-light emitting dental curing lights are used in dental offices to photocure resins in the mouth. In addition, many dental personnel use magnification loupes. This study measured the effect of magnification loupes on the “blue light hazard” when the light from a dental curing light was reflected off a human tooth. Loupes with 3.5x magnification (Design for Vision, Carl Zeiss, and Quality Aspirator) and 2.5x magnification (Design for Vision and Quality Aspirator) were placed at the entrance of an integrating sphere connected to a spectrometer (USB 4000, Ocean Optics). A model with human teeth was placed 40 cm away and in line with this sphere. The light guide tip of a broad-spectrum Sapphire Plus (Den-Mat) curing light was positioned at a 45° angle from the facial surface of the central incisor. The spectral radiant power reflected from the teeth was recorded five times with the loupes over the entrance into the sphere. The maximum permissible cumulative exposure times in an 8-hr day were calculated using guidelines set by the ACGIH. It was concluded that at a 40 cm distance, the maximum permissible cumulative daily exposure time to light reflected from the tooth was approximately 11 min without loupes. The weighted blue irradiance values were significantly different for each brand of loupe (Fisher's PLSD p < 0.05) and were up to eight times greater at the pupil than when loupes were not used. However, since the linear dimensions of the resulting images would be 2.5 to 3.5x larger on the retina, the image area was increased by the square of the magnification and the effective blue light hazard was reduced compared to without the loupes. Thus, although using magnification loupes increased the irradiance received at the pupil, the maximum cumulative daily exposure time to reflected light was increased up to 28 min. Further studies are required to determine the ocular hazards of a focused stare when using magnification loupes and the effects of other curing lights used in the dental office. [ABSTRACT FROM PUBLISHER]

The purpose of this study was to report the surgical outcomes after creating a 120° intentional giant retinal tear for use in removing hemorrhage and subretinal proliferative tissue in patients with polypoidal choroidal vasculopathy (PCV) or age-related macular degeneration (ARMD). This study involved 12 eyes of 12 patients (10 eyes: PCV, 2 eyes: ARMD). After removal of the lens in phakic eyes, we performed a vitrectomy with artificial posterior vitreous detachment. Subsequently, a 120° intentional giant retinal tear was created in the temporal periphery, the retina was then turned, and the subretinal hemorrhage and proliferative tissue were removed. In order to preserve as much of the retinal pigment epithelium (RPE) as possible, we used a bimanual technique under direct visualization. After stretching the retina by use of perfluorocarbon liquid (PFCL), we performed endophotocoagulation around the tear followed by PFCL/silicone oil exchange. Except for 1 eye in which extensive loss of the RPE occurred, the fundus findings and the visual acuity (VA) improved in all patients. In addition, postoperative VA improved to ≥20/50 in 3 eyes in which the macular RPE was preserved. This surgical procedure is an effective treatment for PCV or ARMD patients with extensive subretinal hemorrhage and proliferative tissue. [ABSTRACT FROM AUTHOR]

Abstract: Transpupillary thermotherapy (TTT) is a non-invasive treatment option for malignant choroidal melanoma and choroidal neovascularization (CNV) in age-related macular degeneration (ARMD). It can be considered as a cost-saving treatment, preventing surgical intervention. Up to now the energy level for TTT in CNV has not been clearly defined. Therefore over-treatment (inducing a retinal scar) as well as undertreatment (persistence of CNV) is possible. This may be the main cause for not using TTT as a preferred treatment for wet ARMD. Over the last 2 years the use of TTT for CNV has experienced a slight revival. In some studies a sub-threshold or low-dose TTT has been applied alone or in combination with intravitreal triamcinolone acetonide (iVTA) or vascular endothelial growth factor (VEGF) inhibitors. In several studies TTT for the treatment of malignant choroidal melanoma has been shown to be safe as a unique treatment for small choroidal tumors or as an adjuvant treatment for larger choroidal tumors (‘sandwich technique’). [ABSTRACT FROM AUTHOR]

PurposeThe current medical environment demands that quality health care is delivered at an affordable cost through the use of objective, unbiased clinical data. This study was undertaken to review the current literature on bevacizumab for age-related macular degeneration and its value in determining best clinical practice.MethodsRandomised controlled trials (RCTs) and observational studies that met the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria were identified from the current literature for further analysis. Data concerning treatment dosing regimens, response to treatment, complications, and factors influencing outcome and safety were extracted and compiled into a database.ResultsAs of January 2009, there were 5 RCTs that compared the outcomes of bevacizumab to other treatment options and 50 studies that met the STROBE criteria with similar visual and anatomical outcomes between RCTs and observational studies. Although the doses and dosing frequencies varied between the studies, the mean gain in vision at 3 months was +7.76±5.4 ETDRS letters (range +2 to +14.4); an effect that was maintained at 6 months in studies with longer follow-up. Predominantly classic lesions were the most responsive of all lesion subtypes. The complication profiles/rates were similar to those reported with other anti-vascular endothelial agents.ConclusionsThere is sufficient scientific and statistical evidence to advocate the effective use of OCT-guided administration of intravitreal bevacizumab for neovascular AMD. This is reflected in our study outcome measures that are comparable to findings published from recent well-conducted RCTs on intravitreal ranibizumab at the same time point. [ABSTRACT FROM AUTHOR]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: The complement system is a central part of innate immunity and in its normal setting aimed to recognize and eliminate microbes. For elimination toxic activation products are generated locally and are reported directly of the surface of the invading microbe. A deregulation of the alternative pathway results in defective recognition and toxic activation products can be formed on the surface of host tissues and structures. Recent studies have shown that mutated or defective regulators of the alternative pathway of complement are associated with auto immune diseases of the kidney, including the atypical form of hemolytic uremic syndrome (HUS), membranoproliferative glomerulonephritis (MPGN) and also of the eye, such as age-related macular degeneration (ARMD). Current research provides clues how mutations occurring in genes coding for single complement components or the inactivation of single regulators lead to defective alternative pathway amplification, via the convertase C3bBb. These scenarios explain how defects of a single regulator lead to local, organ specific damage. [Copyright &y& Elsevier]

Abstract: Existing neuropsychological instruments used to clinically diagnose dementia, many of which are based upon visual image processing, do not take into account the different types of sensory loss presented by low vision patients. The purpose of the present study is therefore to assess the effects of low vision on non-verbal neuropsychological test performance. A retrospective chart review identified patients with age-related macular degeneration (ARMD), central vision loss, and an age-matched control group. All participants completed a depression inventory and a «blind» version of the mini-mental Status examination in order to “screen” for dementia. Each group was assessed with a pre-determined battery of non-verbal neuropsychological tests differing in their visual image characteristics (size of test items, contrast, chromaticity, glare, etc.). As expected, preliminary results show a decrease in performance across non-verbal tests for the ARMD group, particularly for tests characterized by visual scanning strategies (Trail Making Test (D-KEFS)) and small item sizes (i.e. Digit Symbol and Symbol Search WAIS subtests). Results demonstrate that ARMD affects performance on certain non-verbal test more than others. All participants will be re-assessed within a 6-week period using the same battery of tests in modified versions (i.e. magnified and polarity reversed). If the implemented visual-test modifications control for decrease in performance due to sensory loss, these adapted tests may be used to compliment existing «blind» cognitive screening presently used to assess low-vision patients, resulting in a more precise assessment of cognitive functioning for this low-vision group. [Copyright &y& Elsevier]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Age-related macular degeneration (ARMD) is the leading cause of blindness in the developed world and yet its pathogenesis remains poorly understood. Retina has high levels of polyunsaturated fatty acids (PUFAs) and functions under conditions of oxidative stress. To investigate whether peroxidative products of PUFAs induce apoptosis in retinal pigmented epithelial (RPE) cells and possibly contribute to ARMD, human retinal pigmented epithelial cells (ARPE-19) were exposed to micromolar concentrations of H2O2, 4-hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE). A concentration- and time-dependent increase in H2O2-, HNE-, and HHE-induced apoptosis was observed when monitored by quantifying DNA fragmentation as determined by ELISA, flow cytometry, and Hoechst staining. The broad-spectrum inhibitor of apoptosis Z-VAD inhibited apoptosis. Treatment of RPE cells with a thionein peptide prior to exposure to H2O2 or HNE reduced the formation of protein-HNE adducts as well as alteration in mitochondrial membrane potential and apoptosis. Using 3H-HNE, various metabolic pathways to detoxify HNE by ARPE-19 cells were studied. The metabolites were separated by HPLC and characterized by ElectroSpray Ionization-Mass Spectrometry (ESI-MS) and gas chromatography-MS. Three main metabolic routes of HNE detoxification were detected: (1) conjugation with glutathione (GSH) to form GS-HNE, catalyzed by glutathione-S-transferase (GST), (2) reduction of GS-HNE catalyzed by aldose reductase, and (3) oxidation of HNE catalyzed by aldehyde dehydrogenase (ALDH). Preventing HNE formation by a combined strategy of antioxidants, scavenging HNE by thionein peptide, and inhibiting apoptosis by caspase inhibitors may offer a potential therapy to limit retinal degeneration in ARMD. [Copyright &y& Elsevier]

The antioxidant action of carotenoids is believed to involve quenching of singlet oxygen and scavenging of reactive oxygen radicals. However, the exact mechanism by which carotenoids protect cells against oxidative damage, particularly in the presence of other antioxidants, remains to be elucidated. This study was carried out to examine the ability of exogenous zeaxanthin alone and in combination with vitamin E or C, to protect cultured human retinal pigment epithelium cells against oxidative stress. The survival of ARPE-19 cells, subjected to merocyanine 540-mediated photodynamic action, was determined by the MTT test and the content of lipid hydroperoxides in photosensitized cells was analyzed by HPLC with electrochemical detection. We found that zeaxanthin-supplemented cells, in the presence of either α-tocopherol or ascorbic acid, were significantly more resistant to photoinduced oxidative stress. Cells with added antioxidants exhibited increased viability and accumulated less lipid hydroperoxides than cells without the antioxidant supplementation. Such a synergistic action of zeaxanthin and vitamin E or C indicates the importance of the antioxidant interaction in efficient protection of cell membranes against oxidative damage induced by photosensitized reactions. [Copyright &y& Elsevier]

Angiogenesis, the development of new blood vessels is a crucial process both for tumor growth and metastatic dissemination. Additionally, dysregulation in angiogenesis has been implicated in the pathogenesis of cardiovascular disease, proliferative retinopathy, diabetic nephropathy, and rheumatoid arthritis (RA). The neuropeptide somatostatin has been shown to be a powerful inhibitor of neovascularization in several experimental models. Furthermore, somatostatin receptors (sst) are expressed on endothelial cells; particularly, sst2 has been found to be uniquely up-regulated during the angiogenic switch, from quiescent to proliferative endothelium. The present manuscript reviews the anti-angiogenic activity of somatostatin and its analogues in neoplastic and nonneoplastic disease. The role of sst subtypes particularly sst2 in mediating its angioinhibitory activity is described. Somatostatin agonists may also exert their anti-angiogenic activity indirectly by inhibition of growth factors like vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis or through its immunomodulatory effects. However, the therapeutic utility of somatostatin agonists as anti-angiogenic drugs in these diseases remains confusing because of conflicting results from different studies. More basic research, as well as patient-oriented studies, is required to firmly establish the clinical potential of somatostatin agonists in therapeutic angiogenesis. The currently available somatostatin agonists have high affinity of sst2 with lower affinities for sst3 and sst5. The emergence of novel somatostatin agonists especially bispecific analogues (agonists targeting multiple cellular receptors) and conjugates (synthesized by chemically linking somatostatin analogues with other antineoplastic agents) with improved receptor specificity signify a new generation of anti-angiogenics, which may represent novel strategies in the treatment of neovascularization-related diseases. [Copyright &y& Elsevier]

Gingival fibroblast cell lines were derived from Sorsby''s fundus dystrophy (SFD) patients carrying the S181C TIMP3 and the E139X TIMP3 mutations. These cell lines were grown in culture to study expression of the wild-type and mutant tissue inhibitor of metalloproteinase 3 (TIMP3) alleles from a normal diploid cell type. Firstly, patient cells were found to co-express the wild-type and mutant TIMP3 alleles, S181C TIMP3 or E139X TIMP3, at the mRNA level using restriction fragment length polymorphism (RFLP) analysis. A SpeI RFLP for E139X TIMP3 is described. Low levels of endogenous TIMP3 protein expression were elevated using the natural polysaccharide calcium pentosan polysulfate (CaPPs) in combination with the cytokine IL-1α. Immunoblotting detected protein expression from both wild-type and mutant alleles, S181C TIMP3 or E139X TIMP3. S181C TIMP3 from these cells was found to dimerise and retain MMP2 inhibitory activity. To facilitate studies of the E139X TIMP3 protein, the allele was expressed using HighFive insect cells. In this cell type, the E139X TIMP3 was synthesised as a mixture of monomer and dimer. Both monomeric and dimeric E139X TIMP3 protein retained MMP2 inhibitory activity in gelatin zymography. Expression of mutant E139X or S181C TIMP3 protein from a normal diploid patient-derived fibroblast cell had no effect on either MMP2 or MMP9 expression or activation whilst transcribed from their normal promoter context. [Copyright &y& Elsevier]