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Purpose: The aims of this work were a) to describe the histology of the lacrimal gland (LG) and cornea induced by an adenovirus (Ad) vector encoding the human erythropoietin (Epo) gene delivered to...

This review is intended to describe the therapeutic approaches for corneal blindness, detailing the steps and elements involved in corneal wound healing. It also presents the limitations of the actual surgical and pharmacological strategies used to restore and maintain corneal transparency in terms of long-term survival and geographic coverage. In addition, we critically review the perspectives of anabolic agents, including vitamin A, hormones, growth factors, and novel promitotic and anti-inflammatory modulators, to assist corneal wound healing. We discuss the studies involving nanotechnology, gene therapy, and tissue reengineering as potential future strategies to work solely or in combination with corneal surgery to prevent or revert corneal blindness.

Purpose: This study aimed to compare the changes in the lacrimal functional unit in the following two models of neurogenic dry eye syndrome: sensory denervation of the cornea versus autonomic denervation of the lacrimal gland. Methods: The neural network supports the lacrimal functional unit. It can be divided into afferent (sensory) and efferent (autonomic) pathways and is affected by severe diseases that compromise the lacrimal functional unit. Male Wistar, 8-week-old rats were divided into the following three groups: 1) control naïve (n=16 animals); 2) autonomic denervation: where rats were subjected to right lacrimal gland nerve ablation and evaluated after 1 and 2 months (1M and 2M) after the procedure (n=7 animals per subgroup, autonomic denervation 1M and autonomic denervation 2M, respectively); 3) sensory denervation induced by 0.2% benzalkonium chloride eye drops, twice a day for 7 days in the right eye (n=10 animals). The corneal sensitivity was measured using the eye wipe test with capsaicin (10 µM). The quantitative real-time PCR was performed to compare the mRNA expressions of proinflammatory cytokines, such as Il-1β, Il-6, Tnf, Mmp9, in the cornea, trigeminal ganglion, and lacrimal gland. In addition, the mRNA of the promitotic factors in the lacrimal gland, such as Bmp7, Runx1, Runx3, Fgf10, and Smad1, was compared. Results: Sensory denervation induced corneal hyperalgesia (p=0.001). Sensory denervation and autonomic denervation increased the mRNA of proinflammatory cytokines in the cornea and lacrimal gland (p

Introduction Olfactory changes are quite common in the population, causing a significant impact on the quality of life. Documentation of the olfactory function is essential for the diagnosis, treatment and follow-up of patients with inflammatory diseases of the upper airways, neurodegenerative diseases or viral infections. Among the different existing smell tests, the CCCRC is an inexpensive test, easy to apply, but it has not yet been evaluated on a large scale in the Brazilian population. Objective To validate the CCCRC smell test, after adaptation for the Brazilian population, evaluating the performance of healthy volunteers and the stability of the test in retests. Methods In this study, we carried out a cultural adaptation of the CCCRC test to Brazil. To validate and determine the normality scores, we applied the test to 334 healthy volunteers, aged >18 years of age. The retest was also carried out in up to four weeks on 34 additional volunteers to assess validity of the results. Results When evaluating the participants’ performance, normosmia and mild hyposmia values were obtained in more than 95% of them. Women (58.4%) showed better accuracy than men (41.6%): p < 0.02, and individuals over 60 years of age showed worse performance (median: 6; 75th percentile: 6.5; 25th percentile). The test and retest of the 34 volunteers demonstrated that there was agreement (ICC, intraclass correlation coefficient) considered good in the left nostril (ICC = 0.65) and excellent in the right nostril (ICC = 0.77) in the combined score. Conclusion The CCCRC test adapted to Brazil showed normal values, similar to the originally-described test and validations in other countries, with a high reproducibility rate. Considering the highly favorable cost-benefit ratio, the adapted CCCRC is a very useful tool for measuring olfactory function in the Brazilian population.

Endocrine disruptors are a group of compounds that occur in increasing amounts in the environment. These compounds change the hormone homeostasis of the target organs regulated by those hormones, mostly by binding to their receptors and affecting their signaling pathways. Among the hormones altered by endocrine disruptors are sex hormones, thyroid hormones, and insulin. Studies have documented abnormalities in the reproductive and metabolic systems of various animal species exposed to endocrine disruptors. Endocrine disruptors can play a significant role in ocular diseases once hormone deficiency or excess are involved in the mechanism of that disease. Cataracts, dry eye disease and retinal diseases, such as macular hole and diabetic retinopathy, are some of the frequent problems where hormones have been implicated. We found that some compounds function as endocrine disruptors in the metabolism of body organs and systems. The increasing frequency of dry eye and other ocular diseases indicates the need to better investigate the potential relationships beyond the isolated associations mentioned by patients and documented as rare case reports. The evidence from case-control studies and experimental assays can provide the information necessary to confirm the endocrine effects of these chemicals in the pathophysiology of dry eye disease. We hypothesize that endocrine disruptors may contribute to the increase of ocular diseases, such as dry eye disease, in recent years.

The burden of corneal blindness and visual deficiency can be felt worldwide. Its association with several endemic diseases such as childhood blindness, trauma, infectious keratitis (including variants caused by herpes, hanseniasis, and fungi), vitamin A deficiency, diabetes mellitus, and other dry eye syndromes reflects its poorly understood underlying mechanisms and suggests that the actual frequency of the disease is underestimated. The low effectiveness of preventive and therapeutic strategies against corneal scarring or deformity predicts a high frequency of patients with corneal blindness in the future. Corneal blindness is associated with environmental factors and socioeconomic limitations that restrain health assistance and maintain a modest efficiency of the current therapeutic strategies for resolving corneal diseases in large-scale programs. We present here a critical review of the concepts associated with corneal blindness that need to be considered when planning strategies to prevent and treat corneal blindness worldwide (to be able to leave Plato’s cave, where corneal blindness is encaged.

Background The pathophysiology of chronic rhinosinusitis (CRS) is still not well known due to the multifactorial etiologies involved. Bacteria play a role in the pathogenesis of CRS by various means, including biofilm adhesion, intracellular persistence, or inducing inflammation secondary to toxins. Endotoxins and exotoxins, especially Staphylococcus aureus superantigens, can produce significant immune responses in the host and are implicated in patients with CRS. The majority of animal models described for CRS revalidates the pathophysiology of acute sinusitis, ostium occlusion, or foreign body associated infection. Objectives To evaluate an experimental model of eosinophilic CRS using prolonged exposure to bacterial toxins. The histological changes in rabbits exposed to S. aureus enterotoxin B (SEB), lipopolysaccharide (LPS), or lipoteichoic acid (LTA) were compared. Methods After induction with ovalbumin (OVA) sensitization with subcutaneous injection for 2 weeks, rabbits underwent surgery to insert an indwelling catheter into the maxillary sinus. The sinus was irrigated with OVA 3 times weekly for 2 weeks, followed by sinus irrigation with bacterial toxin (SEB: 1 µg/mL, LPS: 100 ng/mL, or LTA: 100 ng/mL) 3 times weekly for 4 weeks. The histological changes in the treated sinus were compared with control rabbits. Results Sinuses exposed to bacterial toxins (SEB, LPS, and LTA) produced significant mucosal thickening with infiltration of inflammatory cells, notably eosinophils. SEB was the only toxin that promoted a mixed pattern of inflammation, including eosinophilic and neutrophilic infiltration. Conclusion Our experimental model of eosinophilic CRS in rabbits produced significant mucosal thickening and inflammation in the sinuses exposed to bacterial toxins, with histological changes analogous to what is observed in patients with CRS with nasal polyps. This model may serve as a basis for future investigation of the pathogenesis of eosinophilic CRS in relation to bacterial toxins or as a model for testing new therapeutic modalities for this disease.

Background The management of acute exacerbation of chronic rhinosinusitis (AECRS) is still under debate, especially because there are no adequate studies to support a best-evidence treatment for this condition. Antibiotic use for AECRS has been recommended based on extrapolation of data from acute rhinosinusitis (ARS) or non–placebo-controlled studies. This study aimed to evaluate whether antibiotic therapy modifies the course of AECRS in a randomized, placebo-controlled study. Methods Patients with AECRS were randomized in a double-blinded manner (2:1 ratio) to receive either amoxicillin-clavulanate 875 mg/125 mg twice daily (BID) (AMX-CLAV, n = 21) or placebo capsules (n = 11) during 14 days. All patients were also treated with mometasone furoate and nasal washes with saline. Global sinonasal symptoms (Severity Symptom Assessment [SSA]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), nasal endoscopic score (Lund-Kennedy), and microbiological evaluation were compared to evaluate the efficacy of antibiotic therapy in AECRS. Results Despite the majority of bacteria cultured from the middle meatus swab were sensitive for AMX-CLAV (84%), both AMX-CLAV and placebo-treated groups presented the same clinical course, with no difference between groups. Both groups exhibited overall improvement of symptoms on day 14 compared to day 0 (p < 0.01), especially the items “nasal secretion” and “nasal obstruction” (p < 0.05). We also observed the same evolution of nasal endoscopic and quality of life scores between placebo and AMX-CLAV. Conclusion We concluded that AMX-CLAV for 14 days did not change the clinical course of AECRS compared with placebo. The addition of an oral antibiotic to ongoing topical intranasal steroid spray may not provide additional benefit during management of AECRS.

Purpose The aims of this study were (1) to determine the efficacy of adenovirus vector serotype 5 (Ad) encoding human soluble VEGF receptor 1 (s-VEGFR1) gene transfer to the lacrimal gland (LG); (2) to investigate whether expression of s-VEGFR1 prevents corneal neovascularization (CNV) induced by alkali burns; and (3) to evaluate the safety of the procedure. Methods AdVEGFR1 vectors (25 μL, 1 × 1010 pfu/mL) were injected in the right LGs of rats and were compared with AdNull vector (25 μL, 1 × 1010 pfu/mL) or 25 μL of saline (Control) before cornea alkali burns with 1 M NaOH. After 7 days, CNV was documented at the slit lamp. Tear secretion was measured with phenol red threads. The animals were tested for s-VEGFR1 mRNA and protein in the LG by quantitative (q)PCR and immunohistochemistry staining, respectively. qPCR was used to compare the mRNA levels of IL-1β, IL-6, and TNF-α in the LG and ipsilateral trigeminal ganglion (TG). Results Ad-VEGFR1 transfected 83% (10/12) of the rats. VEGFR1 was present in LG acinar cells. CNV was prevented in 9 of 12 animals in the Ad-VEGFR1 group, compared with the Ad-Null (3:10) and Control groups (1:10) (P = 0.0317). The tear secretion and cytokine mRNA levels in the LG and TG were similar in all three groups (P > 0.05). Conclusions Adenoviral vector gene transfer was safe for LG structure and function. The LG as the target tissue showed local expression of human s-VEGFR1, and CNV was prevented in most of the eyes exposed to alkali burns.

For decades, neurologic and other extra glandular manifestations have been described in Sjögren’s syndrome (SS). More recently, neuropathic, psychological and cognitive alterations are being considered part of the disease. The lacrimal glands (LG), the ocular surface (OS), salivary glands (SG) and the central nervous system (CNS) are integrated to modulate the autonomic functions and, not just those organs, but also the hippocampus, which is linked to the autonomic nervous system, and modulate behavior responses appears to be compromised in the SS. Recent studies confirm that the tryptophan/kynurenine pathway (TKP) can be stimulated by interferon-γ (IFN-γ) and other cytokines, activating the indoleamine-pyrrole 2,3-dioxygenase (IDO) in SS. This pathway interferes on serotonergic and glutamatergic neurotransmission, mostly in the hippocampus, and other structures of the CNS. Although not demonstrated, it is plausible that this constant interference induces clinical signs of SS, and contributes to the discrepancy between symptoms and signs, towards manifestations of hyperalgesia and depression in patients with SS. Therapeutic strategies are being reexamined and new options designed and tested to regulate the involved steps of the TKP. In the future, the application of this concept may offer a clue to the mosaic of manifestations of SS.

Since the first description of microRNAs (miRNAs) in the 1990s, more than 60 papers have described the role of miRNAs on the ocular surface and lacrimal gland (LG). MicroRNAs (miRNAs) have a role in several physiological events and in mediation of disease. They inhibit gene expression by blocking messenger RNA. Diseases such as Sjogren syndrome (SS), ocular surface neoplasias, and infections are known to increase or reduce the expression of specific miRNAs. These miRNAs play key roles in modulating inflammation, delaying or enhancing wound healing, cell differentiation metabolism, and survival. This review describes the current understanding of miRNAs as biomarkers, mediators of diseases, and potential therapeutic targets in ocular surface diseases.

The management of acute exacerbation of chronic rhinosinusitis (AECRS) is still under debate, especially because there are no adequate studies to support a best-evidence treatment for this condition. Antibiotic use for AECRS has been recommended based on extrapolation of data from acute rhinosinusitis (ARS) or non-placebo-controlled studies. This study aimed to evaluate whether antibiotic therapy modifies the course of AECRS in a randomized, placebo-controlled study.Patients with AECRS were randomized in a double-blinded manner (2:1 ratio) to receive either amoxicillin-clavulanate 875 mg/125 mg twice daily (BID) (AMX-CLAV, n = 21) or placebo capsules (n = 11) during 14 days. All patients were also treated with mometasone furoate and nasal washes with saline. Global sinonasal symptoms (Severity Symptom Assessment [SSA]), quality of life (22-item Sino-Nasal Outcome Test [SNOT-22]), nasal endoscopic score (Lund-Kennedy), and microbiological evaluation were compared to evaluate the efficacy of antibiotic therapy in AECRS.Despite the majority of bacteria cultured from the middle meatus swab were sensitive for AMX-CLAV (84%), both AMX-CLAV and placebo-treated groups presented the same clinical course, with no difference between groups. Both groups exhibited overall improvement of symptoms on day 14 compared to day 0 (p0.01), especially the items "nasal secretion" and "nasal obstruction" (p0.05). We also observed the same evolution of nasal endoscopic and quality of life scores between placebo and AMX-CLAV.We concluded that AMX-CLAV for 14 days did not change the clinical course of AECRS compared with placebo. The addition of an oral antibiotic to ongoing topical intranasal steroid spray may not provide additional benefit during management of AECRS.

Spermatozoa of most crustacean species are nonmotile and are packed into spermatophores. In Decapoda, spermatophores are highly variable in morphology and can be useful in the solving of taxonomic and systematic questions, especially among the Anomura. In this study, the morphology and morphometry of the spermatophores of the western Atlantic hermit crabs Pagurus brevidactylus and P. criniticornis are described. The abdomen of fresh male specimens was dissected to expose the reproductive system and to extract the spermatophores, which were analyzed by stereoscopic, light, and scanning electron microscopy. The vas deferens can be divided macroscopically in three regions, all of them containing spermatophores. Tripartite spermatophores are composed of an elongated cylindrical main ampulla, a triangular accessory ampulla, a narrow cylindrical peduncle, and a round pedestal. Dimensions of the spermatophore components are positively correlated to the size of the crab. Morphological patterns observed in this study resemble those of other pagurid hermit crabs investigated to date. The morphological character distribution confirms classifications based on adult morphology and molecular analysis. J. Morphol. 2011. © 2011 Wiley-Liss, Inc.

For decades, neurological, psychological, and cognitive alterations, as well as other glandular manifestations (EGM), have been described and are being considered to be part of Sjögren’s syndrome (SS). Dry eye and dry mouth are major findings in SS. The lacrimal glands (LG), ocular surface (OS), and salivary glands (SG) are linked to the central nervous system (CNS) at the brainstem and hippocampus. Once compromised, these CNS sites may be responsible for autonomic and functional disturbances that are related to major and EGM in SS. Recent studies have confirmed that the kynurenine metabolic pathway (KP) can be stimulated by interferon-γ (IFN-γ) and other cytokines, activating indoleamine 2,3-dioxygenase (IDO) in SS. This pathway interferes with serotonergic and glutamatergic neurotransmission, mostly in the hippocampus and other structures of the CNS. Therefore, it is plausible that KP induces neurological manifestations and contributes to the discrepancy between symptoms and signs, including manifestations of hyperalgesia and depression in SS patients with weaker signs of sicca, for example. Observations from clinical studies in acquired immune deficiency syndrome (AIDS), graft-versus-host disease, and lupus, as well as from experimental studies, support this hypothesis. However, the obtained results for SS are controversial, as discussed in this study. Therapeutic strategies have been reexamined and new options designed and tested to regulate the KP. In the future, the confirmation and application of this concept may help to elucidate the mosaic of SS manifestations.

The striped-legged hermit crab Clibanarius vittatus, with a geographical distribution covering a wide range of latitudes in the western Atlantic, was selected for a comparative study on population features between two different areas of the Brazilian coast that are separated by approximately 3000 km. The two populations were sampled concurrently for nine months. The populations in northern and southeastern Brazil showed different profiles in terms of size of specimens, sex ratio, and shell occupation. The observed plasticity of these life-cycle traits of C. vittatus in relation to local environmental conditions is discussed.

In the Anomura, studies on growth patterns are infrequent, possibly because the heterogeneity of the group, especially in terms of morphology, makes it difficult to construct generalized growth models. Particularly hermit crabs are an interesting group to evaluate aspects of growth, because of their unique body. Isocheles sawayai, a hermit crab found only in the western Atlantic Ocean, poorly known with respect to its sexual dimorphism and maturity, was investigated here based on morphometry. Monthly collections (July 2001 through June 2003) were made from a shrimp fishing boat in the Caraguatatuba region on the northern coast of the state of Sao Paulo, Brazil. The specimens were measured and weighed, and had their sex checked. Throughout the sampling period, 374 specimens of I. sawayai were collected (11.23% nonovigerous females, 6.69% ovigerous females, 79.41% males and 2.67% intersexes). The size at which morphological sexual maturity was reached by both sexes ranged from 4.0 to 4.3 mm shield length, according to the relative growth and the size of the smallest ovigerous female. Sexual dimorphism was shown by males, which were significantly larger than females, and by differences in growth pattern between the sexes, especially for relationships that involved the pleopods, which is related to their different functions in males and females. The present study is one of the first to use pleopod morphometry to determine sexual maturity and dimorphism in hermit crabs, especially for species with intersexuality such as I. sawayai.

We register the occurrence of Isocheles sawayai intersex individuals and analyse their external primary and secondary sexual characters. Specimens were collected monthly from July 2001 to June 2003 from the benthic sand habitat in the Caraguatatuba region of the northern littoral coast of the State of Sao Paulo, Brazil. The sex of individuals was checked based on the position of gonopores and pleopod morphology was also analysed. A total of 374 hermit crabs (297 males, 67 females, and 10 intersexes) was captured and examined. All intersex individuals bore a gonopore on the basis of each coxae of the fifth pereopods as well as male pleopods, associated with gonopores (only one or a pair) on the coxae of the third pereopods. A greater degree of similarity among the analysed sexual characters was observed between males and intersex individuals than between intersexes and females. The results obtained suggest that, at least in this population, intersex individuals are functional males and that hermaphroditism does not play a significant role in the natural history of I. sawayai.