UV Protection in the Cornea: Failure and Rescue

Abstract

Ultraviolet (UV) irradiation induces DNA lesions in all directly exposed tissues. In the human body, two tissues are chronically exposed to UV: the skin and the cornea. The most frequent UV-induced DNA lesions are cyclobutane pyrimidine dimers (CPDs) that can lead to apoptosis or induce tumorigenesis. Lacking the protective pigmentation of the skin, the transparent cornea is particularly dependent on nucleotide excision repair (NER) to remove UV-induced DNA lesions. The DNA damage response also triggers intracellular autophagy mechanisms to remove damaged material in the cornea; these mechanisms are poorly understood despite their noted involvement in UV-related diseases. Therapeutic solutions involving xenogenic DNA-repair enzymes such as T4 endonuclease V or photolyases exist and are widely distributed for dermatological use. The corneal field lacks a similar set of tools to address DNA-lesions in photovulnerable patients, such as those with genetic disorders or recently transplanted tissue.

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

“…Noteworthily, the ocular surface unit needs to be protected from any kind of insult to maintain the corneal functionality [ 54 ]. Recently, increased UV exposure due to ozone thinning has been associated with “dry eyes of environmental origin”, “urban syndrome”, exacerbations of preexisting ocular fibrosis (conjunctival pterygium, photokeratitis, climatic droplet keratopathy), and cataract-genesis, and the current generation is more greatly exposed to UV radiation than earlier ones, due to the increase in unshielded UV rays reaching the Earth’s surface [ 32 , 33 , 34 , 43 , 51 , 54 , 55 , 56 , 57 , 58 ]. This aspect appears of great importance, as the corneo-conjunctival limbus is also populated by mast cells with gatekeeper functions that might react to photo-exposure influencing the local microenvironment [ 57 , 58 ].…”

Inflammasome activation in response to aberrations of cellular homeostasis in epithelial cells from human cornea and retina

“…Direct absorption of UVB energy causes the formation of cyclobutene pyrimidine dimers (CPDs) and the pyrimidine (6‐4) pyrimidone photoproducts [(6‐4) PPs] (Douki & Cadet, 2001; Ikehata & Ono, 2011). CPDs are the most common UVR‐induced DNA lesions and they are formed between two adjacent pyrimidine nucleobases (cytosine and thymine) on the same strand of DNA (Figure 8; Ikehata & Ono, 2011; Song et al., 2014; Volatier et al., 2022). CPD contains a cyclobutene ring, which is formed between the C5 and C6 double bonds of pyrimidines (Douki, 2013).…”

“…Low dose but continuous exposure to UVR produces oxidative stress in the cornea and may accelerate the development of pterygium and different corneal dystrophies such as Fuch's endothelial corneal dystrophy (reviewed in Section 2.2.1) (Ivanov et al., 2018; Soh et al., 2020; Vottonen et al., 2023). In pterygium, the tissue becomes vascularized with fibrotic degeneration on the ocular surface where there is invasive growth from the bulbar conjunctiva onto the cornea (Ivanov et al., 2018; Volatier et al., 2022). UVR is the primary risk factor for pterygium and the incidence of the disease increases with ageing (Volatier et al., 2022).…”

Toxic External Exposure Leading to Ocular Surface Injury

“…UV exposure causes keratitis of the corneal epithelial [ 246 , 247 ]. Acute exposure leads to photokeratitis with conjunctival hyperemia, decreased visual acuity, inflammation, and pain [ 248 , 249 , 250 ]. Fortunately, recovery is usually complete as the cornea will re-epithelialize within a few days.…”