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To report pre and post treatment levels of VEGF-A in the aqueous humour of patients with intraocular tubercular granulomas and study the effect of a combined intravitreal anti-VEGF bevacizumab and moxifloxacin therapy on their regression. Aqueous samples of 10 consecutive patients with intraocular tubercular granulomas obtained before and after initiating treatment were subjected to ELISA for analysing intraocular VEGF-A levels. Intravitreal injections of bevacizumab and moxifloxacin were given weekly till complete regression of these granulomas. All patients received the usual four-drug ATT and oral corticosteroids. Mean baseline VEGF-A level was 1004.27±411.40 pg/ml (401.32-1688.95) that reduced significantly to 27.62±46.86 pg/ml (6.9-131.83) at the last injection. Meannumber of intravitreal injections was 3.1 (2-4). We found significant correlation of decreasing levels of aqueous VEGF-A with the clinical regression of these tubercular granulomas. Intraocular TB granulomas have high levels of VEGF-A. Weekly intravitreal injections of anti-VEGF bevacizumab with moxifloxacin as an adjunct to the standard care may cause prompt regression of tubercular granulomas. TB: Tuberculosis; IOTB: Intraocular tuberculosis; VEGF: Vascular endothelial growth factor; RD: Retinal detachment; Mtb: Mycobacterium tuberculosis; ATT: Antitubercular therapy; AMD: Age-related macular degeneration; SRF: Subretinal fluid; ELISA: Enzyme immunosorbent assay; PCR: Polymerase chain reaction; ONH: Optic nerve head; MDR-TB: Multidrug-resistant tuberculosis; pg/ml: picogram/milliliter; ESR: Erythrocyte sedimentation rate; CECT: Contrast enhanced computed tomography; DNA: Deoxyribonucleic acid; RNA: Ribonucleic acid; BSL: Biosafety level; BCVA: Best corrected visual acuity; HM: Hand movements; KP: Keratic precipitates; PSC: Posterior subcapsular cataract; PS: Posterior synechiae; CRA: Chorio-retinal atrophy; IVMP: Intravenous methyl prednisolone; OCT: Optical coherence tomography; RPE: Retinal pigment epithelium; FFA: Fundus fluorescein angiography; ICG: Indocyanine angiography; RAP: Retinal arterial proliferans. [ABSTRACT FROM AUTHOR]

Apoptosis‐inducing factor (AIF) is a mitochondrial flavoprotein involved in redox signalling and programmed cell death. The role of AIF has been well recognized in diabetes and obesity. However, the aspect of AIF deficiency in the development of hepatic steatosis and liver injury is unknown. Therefore, in the current study, Harlequin (Hq mutant) mouse with markedly reduced content of AIF was investigated to explore the role of AIF on the initiation of liver injury. The wild type (WT) developed physiological and pathological features of non‐alcoholic fatty liver disease (NAFLD) that were not seen in the Hq mice with AIF deficiency, when fed on high fat high fructose (HFHF) diet. Following bile duct ligation (BDL), the liver associated pathological changes were less conspicuous in Hq mice as compared to WT mice. The expression of AIF protein and apoptosis was markedly lesser as compared to their respective control in Hq mice on HFHF diet. Furthermore, the genes involved in fatty acid metabolism were also altered in the group of treated Hq mice. In conclusion, Hq mice failed to develop diet induced hepatic steatosis, suggestive of a role of AIF mediated pathway in the initiation and progression of liver inflammation. Thus, partial loss of AIF appears to be hepatoprotective. Significance of the study: AIF deficiency has multiple roles in altered pathology processes and cellular metabolism, thereby compromising the cellular homeostasis. Considering the molecular functions of AIF in other organ pathology little is known about its role in diet induced liver injury. Hence, the aim of the current study was to investigate the role of AIF deficiency in liver injury and diseases with focus on NAFLD. The study will help to deliniate the mechanisms of NAFLD using Harliquin Mice. [ABSTRACT FROM AUTHOR]

Tubercular granulomas are a common manifestation of intraocular tuberculosis. These are said to be hypoxic granulomas with increased expression of vascular endothelial growth factor (VEGF). Management of these granulomas includes a combination of antitubercular therapy (ATT) and oral corticosteroids. We report a case of tubercular granuloma with exudative retinal detachment which was treated with weekly intravitreal anti-VEGF and antibiotic injections along with ATT and corticosteroids. The VEGF levels measured paralleled with the clinical regression of the granuloma. [ABSTRACT FROM AUTHOR]

The ocular micro-dissection of the rodent eye involves the segmentation of the enucleated eyeball with the attached nictitating membrane, or third eyelid, to obtain the anterior and posterior eyecups. With this technique, the sub-parts of the eye, including the corneal tissue, neural tissue, retinal pigment epithelial (RPE) tissue, and lens, can be obtained for wholemounts, cryo-sectioning, and/or single-cell suspensions of a specific ocular tissue. The presence of the third eyelid presents unique and significant advantages, as it benefits the maintenance of the orientation of the eye, which is important for understanding eye physiology following any localized intervention or in studies involving ocular analysis relating to the eye's spatial topography. In this method, we enucleated the eyeball at the socket along with the third eyelid by carefully and slowly cutting through the extraocular muscles and severing the optic nerve. The eyeball was pierced through the corneal limbus using a microblade. The incision was used as the point of entry, allowing for cutting along the corneal-scleral junction by inserting micro-scissors through the incision point. Small and continuous cuts along the circumference were made until the cups separated. These could be further dissected by gently peeling the translucent layer of the neural retina using Colibri suturing forceps to obtain the neural retina and RPE layers. Further, three/four equidistant cuts were made from the periphery perpendicularly to the optic center until the optic nerve was reached. This opened the hemispherical cups into a floret shape so that they fell flat and could be easily mounted. This technique has been used in our lab for corneal wholemounts and retinal sections. The presence of the third eyelid delineates the nasal-temporal orientation, which allows for the study of various cell therapy interventions post-transplantation and, thus, the targeted physiological validation vital for visualization and accurate representation in such studies.

Acute liver failure (ALF) is a clinical condition caused by various etiologies resulting in the loss of metabolic, biochemical, synthesizing, and detoxifying functions of the liver. In most irreversible liver damage cases, orthotropic liver transplant (OLT) remains the only available treatment. To study the therapeutic potential of a treatment for ALF, its prior testing in an animal model of ALF is essential. In the current study, an ALF model in rats was developed by combining 70% partial hepatectomy (PHx) and injections of acetaminophen (APAP) that provides a therapeutic window of 48 h. The median and left lateral lobes of the liver were removed to excise 70% of the liver mass and APAP was given 24 h postsurgically for 2 days. Survival in ALF-induced animals was found to be severely decreased. The development of ALF was confirmed by altered serum levels of the enzymes alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP); changes in prothrombin time (PT); and assessment of the international normalized ratio (INR). Study of the gene expression profile by qPCR revealed an increase in expression levels of genes involved in apoptosis, inflammation, and in the progression of liver injury. Diffused degeneration of hepatocytes and infiltration of immune cells was observed by histological evaluation. The reversibility of ALF was confirmed by the restoration of survival and serum levels of ALT, AST, and ALP after intrasplenic transplantation of syngeneic healthy rat hepatocytes. This model presents a reliable alternative to the available ALF animal models to study the pathophysiology of ALF as well as to evaluate the potential of a novel therapy for ALF. The use of two different approaches also makes it possible to study the combined effect of physical and drug-induced liver injury. The reproducibility and feasibility of current procedure is an added benefit of the model.