Development and repair of cataract induced by ultraviolet radiation

Background: Several epidemiological investigations show a correlation between cataract development and the dose of ultraviolet radiation (UVR) received. It is experimentally well established that exposure of animal eyes to UVR induces cataract. Most cataracts develop as a gradual increase in lens opacity. Despite this, current estimations of toxicity for cataract are based on the concept that cataract is a binary event. Moreover, current exposure limits for UVR are based on subjective inspections with slit lamp microscopy.

Purpose: The first purpose of the present study was to determine a statistically defined maximum acceptable dose for ultraviolet radiation-induced cataract based on quantitative data of forward light scattering in lenses. The second purpose was to find possible explanations for light scattering by investigating the morphology and the refractive index distribution in the lens. The third purpose was to describe the development of cataract after UVR on the cellular level.

Methods: Six-week-old, female Sprague-Dawley rats received UVR unilaterally in vivo. The radiation from a high pressure mercury lamp was collimated, passed through a water filter and an interference filter or a monochromator (λMAX = 300 nm), and projected onto the cornea. The exposure time was 15 min. The exposure dose ranged between 0.1 and 20 kJ/m2 and the animals were kept between 6 hours and 32 weeks after exposure. The extracted lenses were photographed and forward light scattering was measured. Other methods included light microscopy, fluorescence microscopy, transmission and scanning electron microscopy, freeze-fracture and microradiography.

Results and Conclusions: From a long-term experiment, it was concluded that UVR-exposed lenses scatter light more than their contralaterals and that a higher dose induces more light scattering. After exposure to 5 kJ/m2, the mean forward light scattering remains unchanged between 1 and 32 weeks. Earlier observations, taken together with the current findings, indicate that the optimal time to detect low dose UVR-induced cataract is one week after exposure in rats. The intensity of forward light scattering increases exponentially with increased UVR dose between 0.1 and 14 kJ/m2. Based on this continuous dose-response, a method to determine a maximum acceptable dose to avoid UVR-induced cataract was developed. The statistically defined lower limit of pathologic light scattering is projected on the dose-response function. The dose corresponding to that point can be estimated and was suggested to be called the Maximum Acceptable Dose (MAD). Two low dose UVR exposures with 0 or 6 h intervals between the exposures produce the same degree of lens opacification. When the second exposure follows 24 or 48 h after the termination of the first, lenticular damage increases. Repair processes between 24 and 48 h after exposure appear to be sensitive to UVR, and an additional exposure during this time may aggravate cataract development. Lenses exposed to UVR grow more slowly than their non-exposed contralaterals. This decrease in lens growth was more pronounced with increasing dose. Low doses led to decreased water content in the lens whereas high doses led to swelling. At 6 months after low dose UVR exposure, no global change of the refractive index was found. However, local variations of the refractive index induce a subtle cortical light scattering. In vivo low dose UVR induces programmed cell death which peaks 24 h post-exposure and involves the entire lens epithelium. Dead cells are removed from the epithelium by phagocytosis. This leads to disintegration of the lens epithelium, associated with flake-like opacities at the lens surface. After one week, the epithelium and the equatorial parts of superficial lens fibers contain extracellular spaces. The extracellular spaces together with locally disarranged fibers produce a corrugated opaque lens surface and equatorial opacities. Within several weeks after exposure, the lens epithelium recovers, and new fibers develop normally. The lens fibers regain normal osmotic properties and fill up the extracellular spaces. Repair, however, is incomplete, and disarranged fibers remain in the cortex, producing a subtle shell-shaped opacity. In this way, subtle damage to the lens fibers induced by UVR may accumulate during a lifetime and contribute to the formation of cortical cataract.

List of scientific papers

I. Michael R, Söderberg PG, Chen E (1996). Long-term development of lens opacities after exposure to ultraviolet radiation at 300 nm. Ophthalmic Res. 28(4):209-218.
https://pubmed.ncbi.nlm.nih.gov/8878183

II. Michael R, Söderberg PG, Chen E (1998). Dose-response function for lens forward light scattering after in vivo exposure to ultraviolet radiation. Graefes Arch Clin Exp Ophthalmol. 236(8):625-629.
https://pubmed.ncbi.nlm.nih.gov/9717660

III. Söderberg PG, Michael R, Merriam, JC (2003). Maximum acceptable dose of ultraviolet radiation: a safety limit for cataract. Acta Ophthalmol Scand. 81(2):165-169.
https://pubmed.ncbi.nlm.nih.gov/12752056

IV. Michael R, Löfgren S, Söderberg PG (1999). Lens opacities after repeated exposure to ultraviolet radiation. Acta Ophthalmol Scand. 77(6):690-693.
https://pubmed.ncbi.nlm.nih.gov/10634565

V. Michael R, Vrensen G, van Marle J, Gan L, Söderberg PG (1998). Apoptosis in the rat lens after in vivo threshold dose ultraviolet irradiation. Invest Ophthalmol Vis Sci. 39(13):2681-2687.
https://pubmed.ncbi.nlm.nih.gov/9856778

VI. Michael R, Vrensen GF, van Marle J, Löfgren S, Söderberg PG (2000). Repair in the rat lens after threshold ultraviolet radiation injury. Invest Ophthalmol Vis Sci. 41(1):204-212.
https://pubmed.ncbi.nlm.nih.gov/10634622

VII. Michael R, Brismar H (2001). Lens growth and protein density in the rat lens after in vivo exposure to ultraviolet radiation. Invest Ophthalmol Vis Sci. 42(2):402-408.
https://pubmed.ncbi.nlm.nih.gov/11157874