Source: Zhongshan Ophthalmic Center
Written by: Zhongshan Ophthalmic Center
Edited by: Wang Dongmei

Researchers at Zhongshan Ophthalmic Center of Sun Yat-sen University and University of California, San Diego School of Medicine have shown that acute glaucoma in mice is largely an inflammatory disease and that high pressure in the eye causes vision loss by setting in motion an inflammatory response similar to that evoked by bacterial infections. The study, published in last week's issue of the Proceedings of the National Academy of Sciences (PNAS), has immediate clinical relevance in treating the tens of millions of people worldwide from what is known as acute closed-angle glaucoma.

Professor Zhuo Yehong from Zhongshan Ophthalmic Center of Sun Yat-sen University and Professor Zhang Kang from the University of California, San Diego are co-corresponding authors of this paper. The first authors of the article are from Zhongshan Ophthalmic Center and most of the experimental study is performed in the State Key Laboratory of Ophthalmology in the Center. Professor Zhuo is devoted to the basic and clinical study on glaucoma for nearly 20 years and has a wealth of clinical experience. Their research firstly shows an inflammatory mechanism by which high ocular pressure causes vision loss in acute glaucoma patients.

The second leading cause of irreversible blindness globally, glaucoma refers to a group of eye diseases associated with elevated intraocular pressure broadly classified as either open-angle or closed-angle. Acute closed-angle glaucoma, a common cause of glaucoma in Asia, is a painful ophthalmologic emergency in which there is a sudden rise in eye pressure and immediate damage to eyesight.

In the study, researchers showed that a rapid, sustained large increase in eye pressure in mice turns on a gene (TLR4) that activates a protein known as caspase-8. This signaling protein in turn triggers the production of inflammatory proteins that normally help mammals fight microbial infections. This immune response is a double-edge sword, while these proteins protect human from infection in a normal situation, they also stimulate apoptosis in retinal cells in cases of acute glaucoma.

To further confirm the mechanism linking high eye pressure to retinal damage, researchers showed that they could slow retinal cell death in mice with acute glaucoma by suppressing either the TLR4 gene or caspace-8 protein. The latter is particularly significant because caspace-8 inhibitors are currently in clinical trials for treating cancer and stroke. By injecting these inhibitors into the eyes of acute glaucoma patients, it may be possible to evaluate and bring them vision-sparing treatments more quickly and effectively.