Tauroursodeoxycholic acid preservation of photoreceptor structure and function in the rd10 mouse through postnatal day 30.

PURPOSE: Retinitis pigmentosa (RP) is a progressive neurodegenerative disease resulting in blindness for which there is no current treatment. Although the members of the family of RP diseases differ in etiology, their outcomes are the same: apoptosis of rods and then by cones. Recently, the bile acid tauroursodeoxycholic acid (TUDCA) has been shown to have antiapoptotic properties in neurodegenerative diseases, including those of the retina. In this study the authors examined the efficacy of TUDCA on preserving rod and cone function and morphology at postnatal day 30 (P30) in the rd10 mouse, a model of RP. METHODS: Wild-type C57BL/6J and rd10 mice were systemically injected with TUDCA (500 mg/kg) every 3 days from P6 to P30 and were compared with vehicle (0.15 M NaHCO(3)). At P30, retinal function was measured with electroretinography, and morphologic preservation of the rods and cones was assessed with immunohistochemistry. RESULTS: Dark-adapted electroretinographic (ERG) responses were twofold greater in rd10 mice treated with TUDCA than with vehicle, likewise light-adapted responses were twofold larger in TUDCA-treated mice than in controls at the brightest ERG flash intensities. TUDCA-treated rd10 retinas had fivefold more photoreceptors than vehicle-treated retinas. TUDCA treatments did not alter retinal function or morphology of wild-type mice when administered to age-matched mice. CONCLUSIONS: TUDCA is efficacious and safe in preserving vision in the rd10 mouse model of RP when treated between P6 and P30. At P30, a developmental stage at which nearly all rods are absent in the rd10 mouse model of RP, TUDCA treatment preserved rod and cone function and greatly preserved overall photoreceptor numbers.

Status of the feline retina 5 years after subretinal implantation.

Retinal prosthetics are designed to restore functional vision to patients with photoreceptor degeneration by detecting light and stimulating the retina. Since devices are surgically implanted into the eye, long-term biocompatibility and durability are critical for viable treatment of retinal disease. To extend our previous work, which demonstrated the biocompatibility of a microphotodiode array (MPA) for 10 to 27 months in the normal feline retina, we implanted normal cats with an MPA implant backed with either an iridium oxide or platinum electrode and examined retinal function and biocompatibility for 3 to 5 years. All implants functioned throughout the study period. Retinal function remained steady and normal with a less than 15 percent decrease in electroretinogram response. The retinas had normal laminar structure with no signs of inflammation or rejection in areas adjacent to or distant from the implants. Directly over the implants, a loss of photoreceptor nuclei and remodeling of inner retinal layers existed. These results indicate that the subretinal MPA device is durable and well tolerated by the retina 5 years postimplantation.

Retinal function after subconjunctival injection of carboplatin in fibrin sealant.

PURPOSE: To evaluate retinal function in a rabbit model after subconjunctival delivery of carboplatin in balanced saline solution (BSS) or fibrin sealant to determine possible retinal toxicity. METHODS: One group of rabbits (n = 5) received a unilateral subconjunctival injection of 12.2 +/- 1.0 mg/mL of carboplatin (Paraplatin) in BSS. Another group of rabbits (n = 5) received 25.1 +/- 7.7 mg/mL of carboplatin in fibrin sealant (Hemaseel APR). Rabbits injected with fibrin sealant only (n = 2) and BSS only (n = 2) were used as control groups. Electroretinographic recordings consisted of a series of intensities presented under dark- and light-adapted conditions. Electroretinograms were recorded before the injection (baseline) and 2 days, 1, 2, and 3 weeks after the injection. After 3 weeks, all rabbit eyes were obtained for histopathologic examination. RESULTS: Transient reductions in the dark-adapted b-wave amplitudes were noted 2 days after treatment for eyes injected with carboplatin compared with the vehicle-only treatment groups. Other treatment groups and postinjection time points showed no significant changes from baseline. Retinal structure and thickness were normal 3 weeks after treatment for all treatment groups. CONCLUSION: Subconjunctival delivery of carboplatin in fibrin sealant or BSS does not have a toxic effect on retinal function or structure in a non-tumor-bearing rabbit model at the doses used in this study at 3 weeks' follow-up.