Transcriptome Analysis of Pterygium and Pinguecula Reveals Evidence of Genomic Instability Associated with Chronic Inflammation

Abstract

Solar damage due to ultraviolet radiation (UVR) is implicated in the development of two proliferative lesions of the ocular surface: pterygium and pinguecula. Pterygium and pinguecula specimens were collected, along with adjacent healthy conjunctiva specimens. RNA was extracted and sequenced. Pairwise comparisons were made of differentially expressed genes (DEGs). Computational methods were used for analysis. Transcripts from 18,630 genes were identified. Comparison of two subgroups of pterygium specimens uncovered evidence of genomic instability associated with inflammation and the immune response; these changes were also observed in pinguecula, but to a lesser extent. Among the top DEGs were four genes encoding tumor suppressors that were downregulated in pterygium: C10orf90, RARRES1, DMBT1 and SCGB3A1; C10orf90 and RARRES1 were also downregulated in pinguecula. Ingenuity Pathway Analysis overwhelmingly linked DEGs to cancer for both lesions; however, both lesions are clearly still benign, as evidenced by the expression of other genes indicating their well-differentiated and non-invasive character. Pathways for epithelial cell proliferation were identified that distinguish the two lesions, as well as genes encoding specific pathway components. Upregulated DEGs common to both lesions, including KRT9 and TRPV3, provide a further insight into pathophysiology. Our findings suggest that pterygium and pinguecula, while benign lesions, are both on the pathological pathway towards neoplastic transformation.

Inhibition of cutaneous heat‐sensitive Ca2+‐permeable transient receptor potential vanilloid 3 channels alleviates UVB‐induced skin lesions in mice

“…In this study, we demonstrate the upregulation of TRPV3 expression in mouse model of skin injury induced by UVB radiation, further confirming a causative role of TRPV3 channel activation in UVB induced skin inflammation. A recent study of transcriptome analysis shows that TRPV3 gene upregulation is involved in proliferative lesions of ocular surface caused by ultraviolet radiation, 53 which is consistent with our findings in this study that TRPV3 upregulation is pathologically involved in the development of UV-induced skin inflammation.…”

“…30 In addition, TRPV3 is highly upregulated in both pterygium and pinguecula induced by ultraviolet radiation, but not other TRP channels. 53 These observations further support the dominant role of Ca 2+ -permeable TRPV3 in UV-induced skin injury.…”

“…In the keratinocytes, the regulation of ORAI/STIM‐mediated CRAC channels is involved in UVB‐induced sunburn pain 30 . In addition, TRPV3 is highly upregulated in both pterygium and pinguecula induced by ultraviolet radiation, but not other TRP channels 53 . These observations further support the dominant role of Ca 2+ ‐permeable TRPV3 in UV‐induced skin injury.…”

Nerve Growth Factor (NGF) as Partaker in the Modulation of UV-Response in Cultured Human Conjunctival Fibroblasts

“…As photo-ageing is firmly associated with low-grade and long-lasting exposure, our studies privileged cultures at 5–8 passages (aged sister cells) [ 25 , 35 ]. Some studies reported the modulation of few pterygium-related genes in UV-exposed FBs, reinforcing the link between UV and initiation and/or progression of human pterygium and/or exacerbation of preexisting fibrosis [ 6 , 53 ]. In addition, ocular surface discomfort might also occur in the case of light (UV) reflected from snow, water, and sand [ 33 ].…”

“…The downregulation of some inflammatory and epigenetic factors by NGF might provide new opportunities for the development of targeted therapies. Herein, the interest was double, as most of the chronic exposures to solar UV rays are associated with exacerbation of existing ocular fibrosis (pterygium, pinguecula, squamous metaplasia, or carcinoma) or with some environment-associated dry eye forms [ 32 , 33 , 53 ]. NGF eye drop substitute might represent, in the near future, an alternative for protecting the ocular surface from UV lights [ 3 , 15 , 51 , 58 , 61 ].…”