PREVENTION OF COLLAGEN CROSS-LINKING INCREASES FORM-DEPRIVATION MYOPIA IN TREE SHREW

To examine whether collagen crosslinking is important for the regulati on of refractive development, tree shrews were treated with agents tha t block collagen crosslinking [beta-aminoproprionitrile (beta-APN), or D-penicillamine (DPA)] and underwent monocular deprivation (MD) of fo rm vision by eyelid closure to induce myopia. MD began on the first da y of visual exposure and continued for 75 days. After 15-20 days of vi sual exposure, daily intraperitoneal injections of beta-APN (beta-APN MD animals, n = 5) or DPA (DPA MD animals, n = 5) were administered fo r 17-21 days. beta-APN open animals (n = 5) received the same injectio n schedule, but both eyes remained open. Saline MD animals (n = 5) rec eived i.p. saline and MD. At 75 days of visual exposure, the MD eyes o f beta-APN treated tree shrews were highly myopic (-23.6+/-3.3 D) in c omparison to their open control eyes. This was markedly greater than t he difference in saline MD animals (-11.0+/-0.8 D). DPA MD animals sho wed a relative myopia of -14.3+/-2.2 D. The structural correlate of th e myopia, elongation of the vitreous chamber in the deprived eyes rela tive to the control eyes, was significantly greater in the beta-APN MD animals (0.85+/-0.09 mm) than in the saline MD group (0.44+/-0.03 mm) . The vitreous chamber elongation in DPA MD animals was 0.53+/-0.03 mm , which was not significantly different from the saline MD group. Thin ning of the posterior sclera, but not the cornea, was observed in the deprived eyes of beta-APN treated tree shrews, along with a tessellate d appearance to the fundus. The eyes of the beta-APN open animals show ed no significant differences from normal. beta-APN MD and DPA MD trea ted chickens did nob develop greater myopia or vitreous chamber elonga tion than standard MD chickens. The selective effect of the lathyritic agents on the deprived eyes in tree shrew suggests that collagen cros slinking interacts, in the mammalian sclera, with a retinally-derived signal to regulate the elongation of the eye in myopia.