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Refractive surgery induced epigenetic changes in LASIK and SMILE demonstrate unique signatures and its impact on outcomes

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First Author: S.D'Souza INDIA

Co Author(s):    R. Shetty   P. Khamar   A. Ghosh              

Abstract Details

Purpose:

Refractive surgery such as LASIK and SMILE induce a wound healing response which leads to significant corneal stromal remodelling relevant to obtaining good vision. We have shown that the protein profile immediately post surgery in the stroma changes dramatically. Hence, we studied the epigenetic changes that occur post surgery that may be relevant to long term ECM remodelling.

Setting:

Narayana Nethralaya, India

Methods:

Donor globes(n=20) were obtained from the eye bank for this study.4 globes served as non-surgical controls while SMILE(-6DS) and LASIK surgery(-6DS) was performed on 4 globes each and incubated for 3 days and 2 weeks (n=4 per group per time point).After incubation at 37degC in DMEM media within a humidified incubator, DNA was extracted from the stroma, and were hybridised to an array containing 850,000 CpG methylation sites from the human genome (Infinium Human Methylation 850 EPIC array).Differentially methylated sites were identified by their CpG-level p-values using an FDR <0.05.Gene ontology (GO) analyses were performed for various group comparisons

Results:

A large number of both hypo and hyper methylated CpG sites were observed in both surgeries compared to non-surgical controls. Significantly larger number of CpG sites showed differential methylation in both SMILE and LASIK at 2 weeks compared to 3 days. The GO analysis found MHC proteins, TCR and immunological pathways to be altered. These include chromatin remodellers, HLA proteins, cellular energetics, ECM related transcription factors and proteins. We also found a set of sites and genes that show clear differences between the two kinds of surgeries.

Conclusions:

Our data describe for the first time, the global epigenetic changes in human corneas occurring due to refractive surgery. The data reveal a variety of novel genes and pathways that may have relevance to the development of complications such as ectasia or haze. It also presents the opportunity to utilise drugs that regulate chromatin remodelling for optimal outcomes.

Financial Disclosure:

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