Life Sciences & Biotechnology
Title : | Deciphering predictive and preventative methods in the progression of pterygium using multi-omics approaches |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Daipayan Banerjee, Aravind Medical Research Foundation, Tamil Nadu |
Timeline Start Year : | 2022 |
Timeline End Year : | 2024 |
Contact info : | daipayan@aravind.org |
Details
Executive Summary : | Pterygium is a highly prevalent conjunctival eye disease that causes vision impairment, significantly impacting the quality of life of people, mostly from low socioeconomic status working outdoors. It is characterized by wing-shaped conjunctival fibrovascular overgrowth typically originating from nasal side, migrating towards cornea. In southern India, the incidence rate of pterygium is 25.2 per 100 person-years and adds to ~4% of corneal blindness burden. UV exposure is a critical causative factor of the disease, however, disease etiology remains obscure. Despite the high 12% prevalence rate, there is no pharmaceutical intervention to prevent pterygium progression. Surgical removal is the only treatment option and no prognostic tools to predict disease progression/recurrence exists. Rationale: Dysregulated epigenetic modifications play pivotal role in several disease pathogenesis and are used as biomarker/interventional therapies. It is established that chronic sunlight exposure causes alteration in skin epigenetics and are a causative factor in skin cancer. Pterygium is an ocular surface disease that is constantly exposed to sunlight, however, the role of epigenetic changes and ensuing gene expression changes in pterygium subtypes remains unexplored. We hypothesize aberrant epigenetic modifications regulate gene expression in pterygium pathogenesis and will test in the following objectives. Objective 1: Decipher the role of epigenetic modifications in regulating gene expression in pterygium progression and recurrence. We will employ patient conjunctival tissue /tear samples collected during pterygium excision surgery and use genome-wide DNA methylation profiling, transcriptomics and proteomics profiling approach. Objective 2: Evaluate pharmacological inhibitors and exosomes as adjuvant therapy to prevent pterygium progression. Various modulators (from Objective 1 and preliminary study) will be tested using pterygial fibroblast cell-culture system to evaluate pharmaceutical interventions. Exosomes are extracellular vesicles secreted from cells carrying protein, DNA/RNA cargo to be uptaken by local/distant cell targets, altering the recipient cell’s fate. While their anti-angiogenic and anti-inflammatory effect on injured cornea is known, effect on pterygium is untested. Significance: Pterygium patients are more than 10% of the entire patient population needing eye care from 2010-2019, making pterygium surgery the second-most common surgery after cataract. Evaluating aberrant DNA methylation marks and the corresponding change in gene expression will help devise biomarkers that can predict disease progression. Testing candidate pharmaceutical modulators will identify ways to attenuate disease advancement. The proposal here will not only expand the molecular understanding of the disease pathogenesis but also have a direct clinical implication in pterygium disease management that affects millions of people in India annually. |
Total Budget (INR): | 29,62,440 |
Organizations involved