Research

Kumar’s lab aims to understand the role of the intracellular stress response, specifically the Endoplasmic reticulum and mitochondrial stress, and investigate their crosstalk under normal and pathological conditions. We currently focus on corneal endothelial cells that undergo ER and mitochondrial stress contributing to apoptosis in Fuchs Endothelium Corneal Dystrophy (FECD).

FECD is a genetically complex, heterogenous, age-related degenerative disease of the corneal endothelium cells (CEnCs), characterized by extracellular matrix (ECM) protein deposition or corneal guttae, causing light scatter and accounting for glare and visual complaints in patients. This disease affects approximately 4 % of the USA population over the age of 40, with a higher incidence in Females. Currently, the only treatment for FECD is corneal transplantation, which carries substantial economic, medical, and social burdens. Understanding the disease pathogenesis is essential for developing pharmacological interventions to halt the disease.

In FECD, CEnCs exhibits stress-induced senescence, antioxidant-oxidant imbalance, oxidation of DNA bases, heightened reactive oxygen species (ROS) production, mitochondrial and sustained ER stress. ER and mitochondrial stress are the two major types of intracellular stress factors possibly contributing to endothelium cell degeneration and apoptosis in FECD.

Questions:

Endoplasmic Reticulum and Mitochondrial Crosstalk in Ocular and Neurological Disease

A coherent understanding of ER-mitochondrial crosstalk will aid in the development of specific therapeutic strategies associated with protein misfolding/ER stress, mitophagy, and mitochondrial stress.