Potential therapeutic targets for improving the visual outcomes post refractive surgery

Abstract

Purpose : The corneal tissue injury caused by LASIK and SMILE refractive surgery may lead to distinct wound healing responses. SMILE surgery is thought to reduce the post-operative complications compared to LASIK but the exact molecular factors causing post-surgical complications remain unknown. In this study we identified candidates which modulate the individual responses in SMILE and LASIK post operatively that may have potential therapeutic applications.

Methods : The study was approved by the institutional Ethics Committee and prior written informed consent was obtained from all enrolled subjects. LASIK or SMILE was performed on contralateral patient eyes (n=24). Schirmer’s tear samples were collected pre and post surgery at the interval of 1 (n=12), 3 (n=12) and 6 (n=9) months. Following tear protein extraction, 4-plex ITRAQ labelling was performed and analyzed using Triple TOF LC-MS/MS. Biomechanical analysis was performed through optical coherence tomography (OCT).

Results : A total of 1824 unique proteins were identified across all samples. 92 proteins were found to be differentially regulated across LASIK and SMILE treated eyes. All the values were normalized to the preoperative values of SMILE and LASIK, represented as protein ratios. LCN1 and LTF was significantly upregulated from 1 month to 6 months post operatively in LASIK and SMILE. The expression of Gal-3BP was found to be much higher in SMILE at 1 month (3.4-fold) and 3 months (3.3-fold) when compared to LASIK at 1 months (2.03-fold) and 3 months (1.9-fold). IL-1RA (LASIK 0.9-fold, SMILE 3.34-fold), ANXA1 (LASIK 1.53-fold, SMILE 2.23-fold) and ENO1 (LASIK 1.9-fold, SMILE 3.4-fold) showed higher expression at 6 months in SMILE as compared to LASIK post operatively. PRDX-5 and ACTN1 were downregulated in LASIK (0.89-fold, 0.69-fold) as compared to SMILE (2.35-fold, 1.61-fold) respectively at 6 months. Moreover, CTSB was downregulated in SMILE and upregulated in LASIK across 6 months. In SMILE and LASIK eyes, a significant decrease in stiffness was observed between pre and postoperative states.

Conclusions : Distinct molecular modulators playing a significant role in wound healing post refractive surgery were identified in tears. This study highlights the potential targets (ENO1, CTSB) which may have implications in designing the treatment-based therapeutics in reducing the post op complications.

This is a 2020 ARVO Annual Meeting abstract.