Intraocular pressure fluctuation and neurodegeneration in the diabetic rat retina.

BACKGROUND AND PURPOSE: Early retinal neurodegeneration occurs as one of the complications of diabetes even before clinically detectable diabetic vascular retinopathy. The pathogenesis of retinal diabetic neuropathy is still not well understood. We investigated the serial changes or fluctuations in intraocular pressure (IOP) and examined their roles in the pathogenesis of neuronal degeneration in diabetic retina. EXPERIMENTAL APPROACH: Male Sprague Dawley rats with streptozotocin-induced diabetes were treated with ophthalmic preparations of brinzolamide, latanoprost, both drugs (combined treatment) or saline for 8 weeks. IOP was measured daily under general anaesthesia using a rebound tonometer. Antegrade axoplasmic flow in the optic nerve was assessed with a fluorescent substrate. Immunohistochemical staining, TUNEL assays and western blots were also used. KEY RESULTS: The fluctuation of IOP was higher in the diabetes group than in the normal control or the combined treatment group. Diabetes-induced apoptosis of retinal ganglion cells was decreased by combined treatment. Increased expression of glial fibrillary acidic protein or Iba-1 in the retina or optic nerve head, induced by diabetes, was attenuated only by the combined treatment. Intercellular adhesion molecule-1 was increased in diabetic rats but not in the combined treatment group. Diabetes-induced loss of antegrade axoplasmic transport was partially relieved with combined treatment. CONCLUSION AND IMPLICATIONS: Elevated IOP fluctuations seemed to be associated with the gliosis, neuroinflammation, and neurodegeneration induced by diabetes. The loss of retinal ganglion cells might be relieved by IOP-lowering medication. The improvement of unstable perfusion pressure could play a role in neuroprotection in the diabetic retina.

Effects of aqueous suppressants and prostaglandin analogues on early wound healing after glaucoma implant surgery.

A hypertensive phase frequently develops in the early postoperative period after glaucoma shunt operations. Anti-glaucoma eye drop use is essential when postoperative intraocular pressure (IOP) is not controlled. We investigated whether the use of early topical anti-glaucoma medication affects wound healing following glaucoma tube surgery. Eyes were randomly assigned to receive topical aqueous suppressant (timolol-dorzolamide fixed combination), prostaglandin (PG) analogue (travoprost), or normal saline (control group). First, we observed the effects of topical eye drops on Tenon's tissue in non-operated eyes in rabbits. Second, we examined the effects of these eye drops on rabbit eyes that underwent Ahmed glaucoma drainage device implantation, including the effects on the histopathological appearance of their blebs. Interleukin-2 in the Tenon's tissue was elevated in the PG group when compared to the control and aqueous suppressant groups (P = 0.006). In non-operated eyes, IOP was similar among the groups (P = 0.545). After glaucoma implant surgery, the average height of the inner collagenous layer and the average height of the α-SMA-positive blebs were the least in the aqueous suppressant group (P = 0.013, P = 0.001, respectively) at 4 weeks postoperatively. IOP was lower in the aqueous suppressant group than that in the control and PG groups (P = 0.001) following tube surgery. After Ahmed tube surgery, early treatment with aqueous suppressant decreased fibrosis in the bleb, but early treatment with the PG analogues did not.