Genetic and Environmental Factors in Conjunctival UV Autofluorescence

Abstract

IMPORTANCE Conjunctival UV autofluorescence (CUVAF) photography was developed to detect and characterize preclinical sunlight-induced ocular damage. Ocular sun exposure has been related to cases of pterygia and was recently negatively correlated with myopia. Hence, CUVAF has excellent potential as an objective biomarker of sun exposure. However, much variation in CUVAF has been observed, and the relative contributions of genes and environment to this variation have not yet been identified. OBJECTIVE To investigate sources of variation in CUVAF in relation to its potential clinical relevance. DESIGN, SETTING, AND PARTICIPANTS We performed a cross-sectional analysis of 3 population-based cohort studies in the general community, including the Twins Eye Study in Tasmania, the Brisbane Adolescent Twin Study, and the Western Australian Pregnancy Cohort (Raine) Study. The twin studies were conducted between 2001 and 2009, and the 20-year follow-up of the Raine Study was completed between March 2010 and February 2012. We included genotypic and phenotypic data from 295 Australian families in the Tasmanian and Brisbane twin studies and from 661 participants in the 20-year follow-up of the Raine Study.We compared CUVAF levels in the 3 cohorts and performed a classic twin study to partition variation in CUVAF. We also conducted a genome-wide association analysis to identify specific genetic variants associated with CUVAF. MAIN OUTCOMES AND MEASURESThe total area of CUVAF, heritability of CUVAF, and single-nucleotide polymorphisms (SNPs) associated with CUVAF from the genome-wide association study.RESULTS Within twin cohorts, individuals living closer to the equator (latitude, 27.47°S) had higher levels of CUVAF compared with individuals from southern regions (latitude, 42.88°S) (median [interquartile range], 45.4 [26.8-68.5] vs 28.7 [15.0-42.3] mm 2 ; P < .001). The variation in CUVAF explained by the additive genetic component was 0.37 (95% CI, 0.22-0.56), whereas the variation due to the common environment was 0.50 (95% CI; 0.29-0.71). The SNP rs1060043, located approximately 800 base pairs away from the SLC1A5 gene, a member of the solute carrier family 1, had a genome-wide significant association with a P value of 3.2 × 10 −8 . Gene-based analysis did not improve our power to detect association with other genes. CONCLUSIONS AND RELEVANCEOur findings confirm that, although a large environmental component to CUVAF (equivalent of sun exposure) exists, genes also play a significant role. We identified a SNP (rs1060043) as being significantly associated with CUVAF; replication of this finding in future studies is warranted.

Vitamin D and its pathway genes in myopia: systematic review and meta-analysis

“…Notably, self-report methods used for measuring past outdoor/sunlight exposure are likely to be imprecise and collapsing the data to two categories (high vs low) within the analysis further increases the risk of residual confounding. Yazar and colleagues sought to overcome self-report bias by using conjunctival UV autofluorescence (CUVAF) photography as a marker of cumulative exposure to UV radiation 46. However, the time course of development of damage detected by CUVAF has not yet been well-defined.…”

The use of conjunctival ultraviolet autofluorescence (CUVAF) as a biomarker of time spent outdoors

“…A genetic susceptibility may also promote CUVAF in addition to UV damage acquired through sun exposure. Yazar et al 38 explored the hereditability of CUVAF in twins participating in the Twins Eye Study in Tasmania (n = 146, mean 12 years, range 5-51 years), the Brisbane Adolescent Twin Study (n = 444, mean 19 years, 13-28 years) and singletons recruited in the Raine study (n = 661, mean 20 years,18-22 years). The results indicated that although UV exposure contributed most significantly to CUVAF area, genetics were also associated with CUVAF area after accounting for age and gender.…”

Repurposing blue laser autofluorescence to measure ocular sun exposure

“…The fluorophore responsible for CUVAF is unknown. Lipofuscin, collagen cross‐links, tryptophan, nicotinamide adenine dinucleotide (NADH), or more generally, the presence of altered cellular or mitochondrial activity, have all been suggested as potential sources . Pingueculae autofluoresce strongly on CUVAF imaging and contain elastotic material and advanced glycation end‐products (AGEs), both of which autofluoresce in the cornea and skin .…”

“…Lipofuscin, collagen cross-links, tryptophan, nicotinamide adenine dinucleotide (NADH), or more generally, the presence of altered cellular or mitochondrial activity, have all been suggested as potential sources. 11,18,19 Pingueculae autofluoresce strongly on CUVAF imaging and contain elastotic material and advanced glycation end-products (AGEs), both of which autofluoresce in the cornea and skin. 6,18,[20][21][22][23] Some AGEs form by cross-linking with proteins such as collagen or elastin and UV exposure can speed up this process.…”