Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental Study

Purpose: refractive surgery, such as LASIK and SMILE, induces a wound healing response that leads to significant corneal stromal remodeling. We have shown that the protein profile in the stroma changes dramatically immediately post-surgery. However, the methylation status of the DNA post-refractive...

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Main Authors: Rohit Shetty, Pooja Khamar, Ramaraj Kannan, Puja Thacker, Nimisha Rajiv Kumar, Arkasubhra Ghosh, Vrushali Deshpande
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Life
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Online Access:https://www.mdpi.com/2075-1729/15/2/246
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author Rohit Shetty
Pooja Khamar
Ramaraj Kannan
Puja Thacker
Nimisha Rajiv Kumar
Arkasubhra Ghosh
Vrushali Deshpande
author_facet Rohit Shetty
Pooja Khamar
Ramaraj Kannan
Puja Thacker
Nimisha Rajiv Kumar
Arkasubhra Ghosh
Vrushali Deshpande
author_sort Rohit Shetty
collection DOAJ
description Purpose: refractive surgery, such as LASIK and SMILE, induces a wound healing response that leads to significant corneal stromal remodeling. We have shown that the protein profile in the stroma changes dramatically immediately post-surgery. However, the methylation status of the DNA post-refractive surgery remains unknown. Design/Participants: DNA methylation study. Refractive surgery (SMILE/LASIK) performed on donor eye globes. Method: we investigated the epigenetic changes post-surgery in relation to long term ECM remodeling in an experimental ex vivo study design. Donor globes (n = 19) were obtained from the eye bank. Three globes served as non-surgical controls while SMILE (-6DS) and LASIK surgery (-6DS) were performed on eight globes each and incubated for 3 days and 2 weeks (n = 4 per group per time point). Here, we compared the DNA methylation landscapes of LASIK and SMILE stroma using the Illumina Infinium Human Methylation 850 EPIC array (HM850). Results: significant changes in DNA methylation patterns were observed post-operatively in both LASIK and SMILE groups. Specific genes involved in the activation of actin cytoskeleton and inflammation (<i>smad3</i>, <i>prkca</i> and <i>ssh2</i>) showed hypomethylation in LASIK after 2 weeks and LASIK SMILE after 3 days, respectively, suggesting their active role in corneal repair. The genes (<i>gaa</i>, <i>gstm1</i>, <i>mgat1</i>, <i>galnt9</i> and <i>galnt5</i>) involved in sphingolipid metabolism and mucin biosynthesis showed hypomethylation in SMILE after 3 days. Conclusions: our results suggest that altered DNA methylation patterns may have relevance to the development of complications of haze post-refractive surgery. It also presents the opportunity to utilize drugs that regulate chromatin remodeling for optimal outcomes.
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spelling doaj-art-9cd3ff30bf104d4db0b427c8a5703ebb2025-08-20T02:04:01ZengMDPI AGLife2075-17292025-02-0115224610.3390/life15020246Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental StudyRohit Shetty0Pooja Khamar1Ramaraj Kannan2Puja Thacker3Nimisha Rajiv Kumar4Arkasubhra Ghosh5Vrushali Deshpande6Cornea and Refractive Services, Narayana Nethralaya, Bangalore 560010, IndiaCornea and Refractive Services, Narayana Nethralaya, Bangalore 560010, IndiaGROW Research Laboratory, Narayana Netralaya Foundation, Bangalore 560099, IndiaGROW Research Laboratory, Narayana Netralaya Foundation, Bangalore 560099, IndiaGROW Research Laboratory, Narayana Netralaya Foundation, Bangalore 560099, IndiaGROW Research Laboratory, Narayana Netralaya Foundation, Bangalore 560099, IndiaGROW Research Laboratory, Narayana Netralaya Foundation, Bangalore 560099, IndiaPurpose: refractive surgery, such as LASIK and SMILE, induces a wound healing response that leads to significant corneal stromal remodeling. We have shown that the protein profile in the stroma changes dramatically immediately post-surgery. However, the methylation status of the DNA post-refractive surgery remains unknown. Design/Participants: DNA methylation study. Refractive surgery (SMILE/LASIK) performed on donor eye globes. Method: we investigated the epigenetic changes post-surgery in relation to long term ECM remodeling in an experimental ex vivo study design. Donor globes (n = 19) were obtained from the eye bank. Three globes served as non-surgical controls while SMILE (-6DS) and LASIK surgery (-6DS) were performed on eight globes each and incubated for 3 days and 2 weeks (n = 4 per group per time point). Here, we compared the DNA methylation landscapes of LASIK and SMILE stroma using the Illumina Infinium Human Methylation 850 EPIC array (HM850). Results: significant changes in DNA methylation patterns were observed post-operatively in both LASIK and SMILE groups. Specific genes involved in the activation of actin cytoskeleton and inflammation (<i>smad3</i>, <i>prkca</i> and <i>ssh2</i>) showed hypomethylation in LASIK after 2 weeks and LASIK SMILE after 3 days, respectively, suggesting their active role in corneal repair. The genes (<i>gaa</i>, <i>gstm1</i>, <i>mgat1</i>, <i>galnt9</i> and <i>galnt5</i>) involved in sphingolipid metabolism and mucin biosynthesis showed hypomethylation in SMILE after 3 days. Conclusions: our results suggest that altered DNA methylation patterns may have relevance to the development of complications of haze post-refractive surgery. It also presents the opportunity to utilize drugs that regulate chromatin remodeling for optimal outcomes.https://www.mdpi.com/2075-1729/15/2/246epigeneticsSMILELASIKhypermethylationhypomethylationrefractive surgery
spellingShingle Rohit Shetty
Pooja Khamar
Ramaraj Kannan
Puja Thacker
Nimisha Rajiv Kumar
Arkasubhra Ghosh
Vrushali Deshpande
Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental Study
Life
epigenetics
SMILE
LASIK
hypermethylation
hypomethylation
refractive surgery
title Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental Study
title_full Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental Study
title_fullStr Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental Study
title_full_unstemmed Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental Study
title_short Epigenetic Modulation Directs Recovery Post LASIK and SMILE Surgery: An Experimental Study
title_sort epigenetic modulation directs recovery post lasik and smile surgery an experimental study
topic epigenetics
SMILE
LASIK
hypermethylation
hypomethylation
refractive surgery
url https://www.mdpi.com/2075-1729/15/2/246
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AT nimisharajivkumar epigeneticmodulationdirectsrecoverypostlasikandsmilesurgeryanexperimentalstudy
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