Differentiation Expression of GAP Junction Proteins in Senile Cataract Patients and Aging Mice

Abstract

Purpose : GAP junction channels are formed from connexin protein subunits. Three major connexin protein subunits (Cx43, Cx46 and Cx50) have been shown to play important roles in lens growth, differentiation and maintenance of lens transparency through biochemical and genetic studies using transgenic animals and cell lines. However, aging dependent changes of these proteins in normal and cataract patients have not been individually analyzed. In this study, we report the aging-dependent changes in cataract patients of ages from 50s to 80s, and also compared the expression patterns of these proteins in young and aged mice.

Methods : Automated western immunoblotting was used to analyze the changes of connexin protein subunits (Cx43, Cx46 and Cx50) in individual cataract patients aged from 50-years to 89-years. Over 120 cataract patients were divided into 4 groups: 50-59 years old (50s), 60-69 years old (60s), 70-79 years old (70s) and 80-89 years old (80s). The capsular epithelia isolated during surgical operation were frozen immediately and then used for extraction of total proteins.

Results : From transparent lenses to cataract lenses, Cx43 level is significantly upregulated. In contrast, Cx46 and Cx50 are distinctly downregulated. From 50s to 70s, three types of connexin proteins remain relative stable. However, from 70s to 80s, the levels of the connexin proteins are significantly downregulated. Differences between male and female individually are not statistically significant.

Conclusions : The three types of connexin proteins display distinct changes from transparent lens to cataract lenses, and also age-dependent changes from 50s to 80s. These changes are closely associated with their function alterations which contribute to cataractogenesis (Supported by the grants, #81770910, #81970787, #81900842 and #81970784 from the National Natural Science Foundation of China, the grant, 2019B1515120014 from the Natural Science Foundation of Guangdong Province and the Fundamental Funds,3030901010110 of the State Key Laboratory of Ophthalmology of Zhongshan Ophthalmic Center, and the Graduate Scholarship from Sun Yat-sen University).

This is a 2021 ARVO Annual Meeting abstract.