Vascular endothelial growth factor in diabetic and nondiabetic canine cataract patients.

OBJECTIVE: To measure vascular endothelial growth factor (VEGF) levels in aqueous humor, serum, and plasma in diabetic and nondiabetic cataractous dogs. METHODS: Canine VEGF was assayed in the plasma and serum of 32 dogs (20 diabetics; 12 nondiabetics) and aqueous humor in 57 eyes of those dogs (39 diabetic; 18 nondiabetic) undergoing phacoemulsification, using a commercial canine VEGF assay. Statistical analysis was performed using Fisher's PLSD, t-test, and regression analysis to compare values by diabetic status, duration of diabetes, age, weight, gender, left vs. right eye, and blood clarity. RESULTS: Plasma, but not serum or aqueous humor VEGF values of diabetics were significantly greater than nondiabetics (P = 0.019). Older nondiabetics (10-15 years) had higher plasma VEGF values than younger (0-5 and 5-10 years) dogs (P = 0.0002 and 0.0001, respectively). There was no significant difference in aqueous humor VEGF between left and right eyes in all patients. Serum and plasma, but not aqueous humor, VEGF values in females were significantly higher than males in both groups. CONCLUSION: Similar to human diabetic patients, VEGF aqueous humor values in all dogs are significantly higher than blood values. Aqueous humor VEGF values in human diabetics are elevated and correlate with the severity of diabetic retinopathy. However, aqueous humor values of VEGF in diabetic dogs are not greater than nondiabetics and may serve to protect the dog against development of diabetic retinopathy.

Encapsulated cell-based delivery of CNTF reduces photoreceptor degeneration in animal models of retinitis pigmentosa.

PURPOSE: The objective of the present study was to evaluate the therapeutic efficacy of ciliary neurotrophic factor (CNTF) delivered through encapsulated cells directly into the vitreous of the eye in an rcd1 canine model of retinitis pigmentosa. The dose-range effect of the treatment was also investigated. METHODS: Polymer membrane capsules (1.0 cm in length and 1.0 mm in diameter) were loaded with mammalian cells that were genetically engineered to secrete CNTF. The cell-containing capsules were then surgically implanted into the vitreous of one eye of rcd1 dogs at 7 weeks of age, when retinal degeneration is in progress but not complete. The contralateral eyes were not treated. The capsules remained in the eyes for 7 weeks. At the end of the studies, the capsules were explanted, and CNTF output and cell viability were evaluated. The eyes were processed for histologic evaluation. RESULTS: In each animal, the number of rows of photoreceptor nuclei in the outer nuclear layer (ONL) was significantly higher in the eye that received a CNTF-secreting implant than in the untreated contralateral eye. No adverse effects were observed on the retina in the treated eyes. The explanted capsules produced a low level of CNTF. The cells in the capsules remained viable and densely distributed throughout. CONCLUSIONS: CNTF delivered through encapsulated cells directly into the vitreous of the eye protects photoreceptors in the PDE6B-deficient rcd1 canine model. Furthermore, sparing of photoreceptors appeared dose-dependent with minimum protection observed at CNTF doses of 0.2 to 1.0 ng/d. Incrementally greater protection was achieved at higher doses. The surgically implanted, cell-containing capsules were well tolerated, and the cells within the capsule remained viable for the 7-week implantation interval. These results suggest that encapsulated cell therapy may provide a safe and effective strategy for treating retinal disorders in humans.