Abstract
Purpose :
Pterygium is a benign, fibrovascular growth on the conjunctiva that extends onto the cornea and causes low vision. The associated risk factors are UV radiation, dust, smoke, dryness, eye rubbing. Surgical excision of primary pterygia is related with a high recurrence rate. UVB radiation is a major pathogenic factor in pterygium. Activation of autophagy and its dysregulation as a cellular response to environmental stresses has been linked to ocular surface diseases. Aim of this study to investigate the autophagy regulation and its therapeutic applications for the clinical management of pterygium.
Methods :
45 Primary pterygia and 20 control conjunctiva from donor eye ball were collected. Samples were obtained as a whole pterygium tissue, head, body, and sub-conjunctiva. Human conjunctival epithelial cells exposed to UVB radiation (short and long term) and fibroblast cells from pterygium tissues were analyzed for the expression levels of autophagy related proteins such as LC3, LAMP1, p62, ATG16L, beclin1, cathepsin B, D. Primary fibroblast cells, conjunctival cells exposed to UVB were treated with and without autophagy modulators to check the autophagy dynamics in vitro. Further, primary pterygium fibroblasts were transduced by Lv.CMV.LC3.GFP-mcherry and treated with different autophagy modulators.
Results :
We found decreased expression of autophagy related proteins LC3B, p62, LAMP1, Cathepsin B,D, vATPase, beclin1 and RAB7 in whole pterygium tissues in comparison to control conjunctiva. Additionally, differential expression pattern of autophagy proteins were observed from head, body and sub-conjunctiva of pterygium tissues by immunofluorescence analysis. Human conjunctival cells exposed to UVB and primary fibroblast cells from pterygium showed change in autophagy dynamics. To confirm this, primary fibroblasts were transduced with Lv.CMV.LC3.GFP-mcherry revealed that change in autophagy flux rate which was rescued by addition of autophagy modulators.
Conclusions :
Reduced expression of autophagy related proteins indicates defective autophagy regulation in the pathogenesis of pterygium. Altogether, our data suggest that autophagy dynamics were changed in primary human pterygium. Hence application of autophagy modulating drugs can have potential therapeutic benefit for pterygium treatment.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.