Shared molecular profiles of post-laser vision correction ectasia and keratoconus with key differences in CADPS, CPT1B, CIITA, and TBC1D4

Katarzyna Jaskiewicz-Rajewicz¹Alicja Wysocka¹Magdalena Maleszka-Kurpiel^2,3Eliza Matuszewska-Mach⁴Jakub Wozniak^5,6Rafal Ploski⁷Jan Matysiak⁴Malgorzata Rydzanicz⁷Marzena Gajecka^1,5*

• ¹Institute of Human Genetics, Polish Academy of Sciences, Poznań, Poland
• ²Optegra Eye Health Care Clinic, Poznan, Poland
• ³Chair of Ophthalmology and Optometry, Poznan University of Medical Sciences, Poznan, Poland
• ⁴Chair and Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Poznan, Poland
• ⁵Chair and Department of Genetics and Pharmaceutical Microbiology, Poznan University of Medical Sciences, Poznan, Poland
• ⁶Department of Genetics and Animal Breeding, Poznan University of Life Sciences, Poznan, Poland
• ⁷Department of Medical Genetics, Medical University of Warsaw, Warsaw, Masovian, Poland

Post-laser vision correction (post-LVC) ectasia is a serious complication of 0.033-0.66% of corneal refractive surgeries. Post-LVC ectasia, likewise keratoconus (KTCN) is classified under the "ectatic diseases" category. We hypothesize that, although the mechanistic aspects of post-LVC ectasia and KTCN are distinct, there are notable similarities in the epithelial responses, including shared molecular features. The 11 post-LVC ectasia, 8 mild myopia (controls), and 28 KTCN patients were included in the retrospective multi-omics casecontrol study. CE samples were separated into topographic regions (TRs), central, middle, and peripheral, and 159 experimental samples were subjected to transcriptome (RNA-Seq) and proteome (MALDI-TOF/TOF MS/MS) profiling. Obtained results were verified/validated using RT-qPCR, immunofluorescence staining, and confocal microscopy in the extended sample set (n=21). Residual stromal bed, stromal ablation depth, and percent tissue altered indices best predicted the risk of post-LVC ectasia. Comparing post-LVC ectasia and KTCN, interferon-alpha and interferon-gamma hallmarks were recognized as downregulated in the central and middle TRs of CE of patients with post-LVC ectasia. The downregulation of CADPS gene expression in all three TRs in the extended CE sample set was confirmed. In CE samples, cytoplasmic localization of CIITA and TBC1D4 proteins, the candidate post-LVC ectasia-specific biomarkers, was demonstrated. The assessment of CADPS, CPT1B, CIITA, and TBC1D4 gene expression could enhance the ectasia risk estimation in patients. CE of patients with post-LVC ectasia, apart from differences in transcription and inflammation processes, exhibits similar molecular features to KTCN.