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Mitochondrial ROS Induced Lysosomal  Dysfunction and Autophagy Impairment in an

Animal Model of Congenital Hereditary Endothelial Dystrophy (IOVS, September 2021)

Increased oxidative stress is the major cause of corneal endothelial cell death in CHED. I was interested in finding out whether

oxidative stress affected other organelle functions, and if I can identify medical therapies to alleviate the disease progression.

Major findings 

1) Oxidative stress causes dysfunctional lysosomal activity and autophagy impairment.

2) Treatment with MitoQ, an oxidative stress quencher, decreased all the major disease symptoms.

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Lysosomal acidification is reduced in Slc4a11 KO corneal endothelial cells. It is restored with MitoQ treatment.

Anterior segment OCT images show corneal thickness.

With MitoQ treatment, a significant reduction in corneal thickness

was noted in the Slc4a11 KO CHED mouse model. 

Current Projects

My postdoctoral work is on Congenital Hereditary Endothelial Dystrophy (CHED).

CHED is a rare disease that arises because of the loss of function of a gene, Slc4a11. It results in corneal edema,

endothelial cell death and causes irreversible blindness. The only treatment is corneal transplantation.

Young animals

Older animals

Decreased corneal edema in young (5 weeks old) Slc4a11 KO animals with AAV9-Slc4a11 anterior chamber injections.

AAV9-Slc4a11 prevented corneal edema from worsening in the older animals (11 weeks old).

Rescue of the CHED Mouse Model by AAV-mediated Slc4a11 Replacement (Ophthalmology Science, In Press)

A potential treatment avenue not explored in CHED and other corneal endothelial dystrophies is gene therapy.

In the current study, I asked if gene therapy can reverse the disease-associated phenotypes in CHED.


Major Findings

1) Gene therapy can reverse the major disease-associated phenotypes in the CHED mouse model

2) Earliest interventions offer the most benefit from disease progression.

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