Fungal Keratitis

Our group is perhaps the largest group working on fungal infection of the eye in India as well as across the globe. In India, fungal infections contribute to more than 50% of infectious keratitis, with Fusarium and Aspergillusflavus being the two important etiological agents. Agricultural workers are the major group affected by this infection primarily due to their frequent exposure to fungal spores and accidental trauma to the eye.

We adopt a comprehensive OMICS approach to decipher and understand the pathogenesis of mycotic keratitis, at the level of both the human host and the fungal pathogens.  On the host side, proteomics of tear and cornea helped unravel the major events/pathways activated in the human host in response to the fungal infection.  We have also identified many proteins in the tear fluid as indicators of the severity of the infection.  We are currently validating many of these tear markers to develop a method to predict the prognosis of the fungal ulcer. Genomics, transcriptomics and proteomics of the fungal pathogens has led to a comprehensive understanding on inter- as well as intra-species difference among the fungal pathogens.

Diabetic Retinopathy

Diabetic retinopathy (DR) is one of the most common microvascular complication in diabetic and is a leading cause of vision loss among working-age adults in the world. The clinical classification of DR is graded into two major groups, non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). The main cause of visual impairment in DR is the development of diabetic macular edema (DME) and PDR.

Our research focuses on identifying DR-specific protein biomarkers with diagnostic or prognostic value.  Towards this, we have examined the proteome of both serum and vitreous to identify proteins that show significant alterations with reference to the disease stage and/or disease progression.  In addition to the serum proteins, we also analyse the proteomeof microparticles (vesicles secreted by different cell types in the body) circulating in the serum for identification and validation of DM and DR-specific protein markers.   Through an Indo-UK collaborative project, we are currently validating a panel of selected serum markers in both Indian and UK population.  Through these biomarkers studies, we aim to identify diagnostic markers that will help identify DM patients at high risk of developing DR as well as prognostic markers that will predict the disease progression among DR patients.

Glaucoma

Primary Open Angle Glaucoma (POAG) is the second leading cause of blindness worldwide, contributing to 12% of world blindness.  POAG is asymptomatic and the loss of vision is irreversible. Proteome analysis of aqueous humorfrom POAG patients in comparison with that of cataract control enabled the identification of POAG related protein changes.  These proteins will be validated in a larger patient cohort to develop a panel for diagnostic or prognostic use.

Pseudoexfoliation glaucoma is yet another glaucomatous condition that is quite prevalentand  nearly 25-35% of the PEXS patients develop glaucoma in India.  There is no treatment available for PEXS as the source and mechanism of formation of PEX material is currently unclear.  To address this gap in knowledge, we are examining the role of iris tissue in the pathogenesis of PEX disease.

Keratoconus

The major objective of this project is the development of a novel chemical cross-linker for the treatment of keratoconus. The novel chemical cross-linker aims to overcome the removal of epithelium and the pain associated with the patients while undergoing conventional UV-Riboflavin cross-linking treatment. This is a collaborative project between AMRF, University of Liverpool and Aurolab. The novel chemical cross-linker has exhibited negligible cytotoxicity to the porcine and human corneas. It has shown optimal penetration into the stroma of the cornea to induce significant increase in the stiffness of the cornea without altering its morphology. The mechanism of action of the novel cross-linker is being analysed in a separate study. The cross-linker formulation has shown great promise for further trials and formulation. The ultimate clinical formulation will be done by Aurolab.

Pterygium

Pterygium is a benign, chronic triangular overgrowth of fibrovascular conjunctiva growing from the nasal side of the conjunctiva onto the cornea. It is a common condition globally with approximately 13% prevalence in Indian population that increases to about 25% in the elderly. Although benign, this abnormal growth protrudes towards the cornea, impairs vision and ultimately affects the quality of life.

In the absence of any medical intervention, surgical removal of the pterygium outgrowth is the only definite treatment constituting the standard of care. Invasive surgical procedure, cost of surgery and high recurrence rate are deterrent factors that affects patient compliance.  Thus, there is an urgent need to find a druggable target that can preclude the need for surgical intervention in pterygium treatment. While pterygium has been strongly associated with ultraviolet light exposure and evidence implicates several divergent mechanisms like anti-apoptotic factors, immunological, cytokines, growth factors, extracellular matrix (ECM) modulators, genetic factors, viral infection as possible causative, the etiology of this disease is still elusive.

We are employing proteomics and transcriptomics approaches using conjunctival samples from patients collected during pterygium surgery to identify pathways that contribute to pterygium progression. The long term goal is to halt pterygium progression by impeding these pathways using small molecule pharmacological inhibitors.

Ongoing Projects

• Project title: Proteome profiling of serum microparticles in diabetes and diabetic retinopathy patients: Towards identification and validation of predictive biomarkers – Funding: Department of Health Research, Govt of India
• Project title: Prospective Multicenter discovery and validation of diagnostic circulating and urinary biomarkers and development of sensor(s) to detect sight threatening diabetic retinopathy: Biomarker and Biosensor study in UK and India  (Work Package 3) – Funding: Research Councils UK
• Project title: Prediction of Treatment Outcome in Fungal Keratitis Patients– Funding: Cognizant Foundation
• Project title: Development of aptamer-based assays for diagnosis of infectious keratitis and absolute quantitation of proteoform markers of diabetic retinopathy  – Funding: Sun Pharma
• Project Title:Screening the Kadaladi family with early onset Glaucoma for Myocilin gene mutations – Funding : Sun Pharma
• Project Title: Understanding the mechanism of action of a novel chemical cross-linker designed to treat keratoconus – Funding : ICMR
• Project Title: Identification of druggable targets for attenuating the progression of pterygium development – Funding: Sun Pharma
• Project Title: Role of Retinol Binding Protein 3 (RBP3) in progression of Diabetic Retinopathy (DR) and evaluate its potential as a DR biomarker in Type 2 diabetic patients – Funding: VISTA

Faculty

• Prof. K. Dharmalingam, Director – Research
• Dr. Jeya Maheswari, Scientist
• Dr. O.G. Ram Prasad, Scientist
• Dr. Daipayan Banerjee, Scientist 1

Clinician Scientist

Research Scholars