Abstract
Abstract: :
Purpose: To determine the efficacy and safety of cyclodialysis, a surgical procedure for lowering intraocular pressure (IOP) in rats, and its potential for limiting optic nerve damage in animals with experimental obstruction of aqueous humor outflow. Methods: Brown Norway rats, 32 normal (5-, 8- and 24-months-old) and 9 (8 month-old) with elevated IOP following episcleral vein sclerosis were used in these studies. Cyclodialysis over the superior 1 to 3 clock hours was performed unilaterally using a blunted needle in conjunction with a small amount of viscoelastic material to separate the ciliary body from the scleral spur. Awake IOP was measured daily prior to and after the procedure. To stabilize circadian IOP fluctuation, rats were housed in constant light. Eyes were collected and optic nerve cross sections prepared for masked nerve injury grading by light microscopy. Neurofilament H mRNA quantitation by RT PCR was used to assess retinal ganglion cell responses. Results: Cyclodialysis in normal eyes resulted in 40±3% reduction in IOP, compared to untreated fellow eyes. For 5- and 24-month-old groups (N=14 each), tissues were collected following both 3 and 6 months of lowered IOP. Repeat cyclodialysis was performed as necessary to maintain IOP below 20 mm Hg, averaging 1.5 procedures per eye. Cyclodialysis and untreated groups had mean nerve injury grades of 1.18±0.38 and 1.06±0.11, respectively (p=0.12), although two cyclodialysis eyes (7%) had small focal nerve lesions. There was no detectible difference in IOP response to cyclodialysis between old and young animals. Cyclodialysis in 8-month-old animals (N=11) did not affect retinal neurofilament H mRNA levels, which were 94±12% of fellow eye values (p=0.83). Cyclodialysis in animals with experimental aqueous humor outflow obstruction resulted in a 20.1± 8.3 mm Hg (43± 17%) reduction in IOP, when compared to the mean IOP immediately prior to cyclodialysis (46.3±2.5 mmHg). Optic nerve injury analysis showed that 67% of the optic nerve cross sections from these cyclodialysis eyes displayed focal, rather than complete, optic nerve lesions. Prolonged IOPs above 40 consistently result in complete optic nerve degeneration. Conclusions: Cyclodialysis provides a reliable, simple method of lowering IOP in both normal eyes and eyes with elevated IOP. In the latter animals, this IOP lowering appears to limit the severity of optic nerve degeneration. Cyclodialysis will be a useful adjunct to this glaucoma model for studying injury mechanisms and neuroprotective therapies.
Keywords: animal model • intraocular pressure • neuroprotection