UVB promotes the initiation of uveitic inflammatory injury in vivo and is attenuated by UV-blocking protection

Abstract

Purpose: Uveitic inflammatory injury can cause irreversible visual loss; however, no single animal model recapitulates all the characteristics of human uveitis. Ultraviolet radiation (UVR) is one of the risk factors for uveitis, but the role of UVR in the pathogenesis of uveitic injury is unclear. The aim of this study was to elucidate whether UVB promotes the initiation of, and subsequently contributes to, uveitic inflammatory injury.

Methods: Mice were assigned to either a blank control group or one of three UVB treatment groups: no protection, protection with Nelfilcon A contact lens (Food and Drug Administration [FDA] class II, about 46.8% UVB transmittance), or protection with Etafilcon A contact lens (FDA class IV, about 0.55% UVB transmittance). The contact lenses acted as blocking barriers against UVR. After the application of UVR, pathologic injuries were determined with slit-lamp microscopy and histologic examination.

Results: Compared with the intact status of the controls, the anterior eyes of the UVB groups showed pathologic alterations in physiologic properties and tissue integrity. UVR promoted anterior uveitic inflammatory injury, with expansion of the hyperemic iris vessels, over-production of aqueous humor protein, disruption of the blood-aqueous barrier, and embedding of infiltrative leukocytes inside the iridocorneal angle. However, blockage of UVR in vivo retarded the progression of uveitic inflammatory injury. The highest level of UV protection in the Etafilcon A group resulted in greater inhibition of uveitic inflammatory injury than that in the Nelfilcon A group.

Conclusions: This study demonstrates that UVB initiated and promoted uveitic inflammatory injury. UV protection is needed for the clinical management of anterior uveitis. The Etafilcon A lenses provide better protection of the anterior segment of the eye against UVB damage compared with the Nelfilcon A lenses.

Figure 1

Experimental design. A: Daily ultraviolet B (UVB) light exposure (arrowhead) was performed for 7 days. No protection was given to the UVB group. The Etafilcon A and Nelfilcon A groups were provided protection by the contact lenses before exposure to ultraviolet radiation (UVR). B: The properties of the contact lenses used in this study. C: The UV transmittance properties of the Etafilcon A and Nelfilcon A contact lenses.

Figure 2

UVR role in the pathogenesis of corneal and uveitic injury in anterior eye segments. The clinical corneal evaluation of (A-D) corneal smoothness, and (E-H) lissamine green staining. I: Quantitative analysis of corneal smoothness (n = 12 per group). J: The incidence of corneal smoothness (score>2). K: Quantitative analysis of lissamine green staining (n = 12 per group). L: The incidence of corneal staining (score >2). M-P: The clinical evaluation of anterior iris surface. N,O: The hyperemic change in the vessel on the anterior iris surface (arrowhead) and limbus (arrow). Q: Quantitative analysis of the clinical uveitis score (n = 12 per group). R: Quantitative analysis of the aqueous humor protein concentration (n = 7 per group). All scale bars = 1.25 mm. p<0.05; p<0.01.

Figure 3

UVR contribution to the pathogenesis of cellular infiltrates in the iridocorneal angle of eyes. A-H: Histological analysis of anterior eye. B, C: The influx of PMNs in the corneal stroma (indicated by arrow), and (F, G) iridocorneal angle (indicated by arrow). I: Quantitative analysis of PMNs in the corneal stroma (n = 11 per group). J: The incidence of corneal inflammatory injury (n = 11 per group). K: Quantitative analysis of PMNs in the iridocorneal angle (n = 11 per group). L: The incidence of uveitic inflammatory injury (n = 11 per group). M, N: Scatterplots indicated a significant correlation between the reduction in UVR strength and PMN recruitment inhibition. Scale bars: 25 μm. The p<0.05 and p<0.01 indicated the statistically significant.

Figure 4

Contribution of MMP-9 protein produced by infiltrating leukocytes to uveitic inflammatory injury after UVR. Both lenses, Etafilcon A (right eye; A-E) and Nelfilcon A (left eye; F-J) contralaterally performed evaluation in a same mice to investigate the relative damage and protection after UVR. The arrowhead in H indicate the hyperemic iris. The arrow in I and J indicate the infiltrating leukocytes. K-R: The expression of MMP-9 protein was found in the infiltrating leukocytes of corneal stroma (P), anterior chamber (L, N), and iridocorneal angle (P, R) after UVR. S: The protein levels of MMP-9 was evaluated by western blotting. T: Quantitative analysis of MMP-9 protein in the anterior segment of eye (n=4 per group). Scale bars: 25 μm. The p<0.01 indicated the statistically significant.