The L V Prasad Eye Institute (LVPEI) was established in 1987 at Hyderabad by Gullapalli Nageswara Rao as a not-for-profit, non-government eye care institution. The mission of LVPEI is to provide "equitable and efficient eye care to all sections of society." The institute was founded by Dr. Gullapalli Nageswara Rao.
To develop gender and refractive error stratified percentile curves for anterior and posterior ocular biometry components of Indian school children based on age. A retrospective analysis of 2168 Indian school children (aged 10–17 years) was conducted. Right eye percentile curves for spherical equivalent refraction (SER), axial length (AL), average keratometry (K), axial length to corneal radius of curvature (AL/CRC) ratio, central corneal thickness (CCT), anterior segment length (ASL), lens thickness, posterior segment length (PSL) and posterior segment length to anterior segment length (PSL/ASL) ratio were generated with the Lambda-Mu-Sigma method. The overall data were categorised into myopes (uncorrected visual acuity ≥0.10 logMAR and SER ≤ − 0.75 D) and non-myopes (including those with emmetropia, hyperopia and astigmatism) based on non-cycloplegic autorefraction values. Overall, the AL, ASL, PSL and AL/CRC ratios were higher at 17 than 10 years of age (p ≤ 0.01), while the average K, CCT, LT and PSL/ASL ratios showed no significant difference. At 10 and 17 years, the respective 50th (2nd, 98th) percentile for AL was 23.09 (21.52, 24.72) mm and 23.74 (22.18, 26.43) mm in males and 22.37 (21.16, 23.76) mm and 23.07 (21.37, 26.34) mm in females. The 98th percentiles for AL, PSL and AL/CRC ratio (across all age groups, including both genders) in non-myopes spanned between the 75th and 90th percentiles in myopes. For emmetropes, AL percentiles (50th (2nd, 98th)) were 22.58 (21.26, 23.96) mm at 10 years and 23.20 (21.55, 25.18) mm at 17 years of age. AL, PSL, ASL and AL/CRC ratio increased with age, while other parameters showed no significant variation. Significant gender-based differences were found between AL percentiles and for refractive groups. The significant overlap between myopes and non-myopes suggests that AL and AL/CRC ratio percentiles alone may have limited discriminatory value between refractive groups in a cross-sectional clinical setting.
Type 2 diabetic (T2D) individuals are predisposed to enduring vascular complications despite therapeutic/lifestyle intervention due to 'metabolic memory', an epigenetic reprogramming in various cell/tissue types. The present study examined the potential role of DNMT isoforms in regulating glucose-induced metabolic memory and associated changes in endothelial metabolism leading to diabetic complications. The study involved micro/macro vascular endothelial cells (ECs), high-fat diet (HFD)-induced diabetic mouse models, and subjects with diabetic retinopathy (DR) at varying enforced levels of glycemia. Immunoblotting and HPLC-based analysis were performed to examine the expression of DNMT isoforms and global DNA methylation levels. Reactive oxygen species (ROS) and inflammatory mediators were analyzed by Spectramax and multiplex ELISA respectively. Cell cycle analysis and angiogenesis assays were performed by flowcytometry and 3D spheroid assays. Integrated omics analysis using LC-MS and RRBS was performed to identify metabolic and epigenomic signatures of metabolic memory. Candidate genes were validated in clinically characterized individuals with DR by RT-PCR. High glucose and AGEs persistently elevated expression of the DNMT1 but not DNMT3A and DNMT3B despite glucose normalization. Global DNA methylation, DNA synthesis, angiogenesis, oxidative stress, inflammatory mediators, and nucleotide metabolism intermediates were elevated and sustained despite glucose normalization. Metabolic memory was associated with differential methylation of genes associated with vascular functions and nucleotide metabolism. We observed persistent DNA methylation of IMPDH2, the rate-limiting enzyme of purine metabolism. DNMT1 and IMPDH2 were elevated in retinal and umbilical vein endothelial cells in vitro, as well as retinal and aortic tissues of the HFD mice despite dietary intervention, which were reduced upon treatment with 5-aza-2'-deoxycytidine. IMPDH2 transcripts were elevated in subjects with DR undergoing antidiabetic therapy and in the exosomes derived from the vitreous of subjects with proliferative DR. Mycophenolate mofetil, a pharmacological inhibitor of IMPDH2, decreased sustained levels of DNMT1 and impeded sprout formation in 3D endothelial cultures induced by transient hyperglycemic conditions. Our study provides novel insights into the biology of metabolic memory by identifying IMPDH2 regulated by DNMT1 during epigenetic and metabolic reprogramming, with clinical relevance to the pathogenesis of DR.
Purpose:Calcium (Ca2+) is involved in regulating many cellular functions, including the intercellular barrier integrity. This study investigated the expression, localization, and permeability of TRP-Vanilloid (TRPV1-4) channels to Ca2+ in human corneal endothelial (hCE) cells. Methods:Gene and protein level expression of the TRPV1 to 4 channels was determined by PCR, immunostaining, and Western blot analysis in hCEs from fresh human donor tissues and cultured primary cells. Colocalization of the channels with actin and junction proteins zonula occludens-1 (ZO-1) and N-cadherin was quantified by calculating Pearson's coefficient using ImageJ software. Changes to Ca2+ influx in response to channel-specific agonist and antagonist treatment were measured using Fluo-4 AM dye. Results:TRPV1 to 4 expression was confirmed in cells by PCR and Western blot. Staining revealed distinct membrane and cytoplasmic localization of these four channels. All four channels showed high colocalization with N-cadherin (r ≥ 0.7), whereas TRPV4 colocalized with N-cadherin and ZO-1 equally (r ≥ 0.8). An increase in Ca2+ influx was noted in >80% of the cells when TRPV1, TRPV2, and TRPV4 channels were activated using channel-specific agonists. A similar response was evident in only 50% of cells following TRPV3 channel activation. Pretreatment of cells with antagonists reduced agonist-induced Ca2+ influx, as noted by a significant reduction in the area under the curve of the influx profile, relative to agonist treatment. Conclusions:This study confirms TRPV1 to 4 expression, enumerates their distinct localization and colocalization with junction proteins, and their permeability to Ca2+ in hCEs. Taken together, these results suggest a potential role for these channels in maintaining Ca2+ homeostasis and barrier function in these cells.
PurposeTo describe the demographic profile and clinical features associated with upper eyelid (UL) hyperlaxity in the Indian subcontinent.MethodsRetrospective chart review of 100 consecutive patients with UL hyperlaxity, presenting at a tertiary eye centre in India, between January 2016 to February 2022. The data collected included the demographics, clinical features including the ophthalmic and systemic manifestations, and management outcomes.ResultsThe average age at presentation was 42.71 (±18.73) years. Majority were males (83%). Syndromic associations included Down's syndrome (2%) and Ehler-Danlos syndrome (1%). Of the 45 investigated, obstructive sleep apnea was diagnosed in 24% cases. Adnexal manifestations included concurrent lower eyelid laxity (70%), blepharoptosis (41%) of which 38% were aponeurotic, lower eyelid retraction (37%), chalazia (25%) of which 58% were either recurrent, multiple, or both, lacrimal gland (LG) prolapse (11%), lash ptosis (11%), lower eyelid ectropion (8%), entropion (5%), and recurrent dacryoadenitis (3%). Chronic papillary conjunctivitis (66%) was the most common ocular surface abnormality followed by meibomian gland dysfunction (31%). Seven cases (7%) had eyelid imbrication syndrome (EIS), of which 60% had retinopathy of prematurity. Surgical management was recommended in 25% cases, indications being ptosis (13%), generalized eyelid laxity (11%), and recurrent globe luxation (2%).ConclusionUL hyperlaxity can be associated with a myriad of ophthalmic manifestations. One should look for novel findings such as EIS, dacryoadenitis, LG prolapse, and lower eyelid retraction in these cases.
