Purchase this article with an account.
N.P. Cheruvu, A.C. Amrite, U.B. Kompella; Effect of Eye Pigmentation and Diabetes on Transscleral Drug Delivery . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4470.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine whether eye pigmentation and diabetic state influence transscleral retinal delivery of celecoxib, a drug capable of reducing retinal VEGF expression and vascular leakage in diabetic rats.
To study the effect of pigmentation, celecoxib (3 mg/rat) suspension was injected subconjunctivally in both Sprague Dawley (albino, SD) and Brown Norway (pigmented, BN) rats, in one eye. The animals were sacrificed at 0.25, 0.5, 1, 2, 3, 4, 8, and 12 hours, the blood was collected, and the eyes were enucleated and frozen. To study the effect of diabetes, the above procedure was repeated in both the strains following two months of diabetes induction with an intraperitoneal streptozotocin injection. The sclera, choroid–RPE, retina, vitreous, lens, and the cornea were isolated from the frozen eyes and celecoxib was quantified using an HPLC assay. From the tissue concentrations (µg/g tissue) of celecoxib, the area under tissue concentration time curve (AUC0–12, µg.hr/g tissue, mean ± sd for n = 4) was determined.
The plasma AUCs showed no significant differences between the SD and BN rats for normal as well as diabetic groups. The AUCs in the avascular tissues such as sclera, cornea, and lens also did not differ significantly between the various groups. Effect of pigmentation: The AUC for the ipsilateral pigmented choroid–RPE (133 ± 16) was approximately 1.5–fold higher compared to albino choroid–RPE (91 ± 15). The effect of pigmentation was more apparent in the contralateral eyes, with the choroid–RPE AUC in the pigmented rats (42 ± 2) being 3.5–fold higher compared to albino (12 ± 0.9) rats. The AUC for the ipsilateral albino retina (503 ± 64) and vitreous (304 ± 40) were approximately 3– and 4.5–fold higher compared to the ipsilateral pigmented retina (163 ± 16) and vitreous (68 ± 8), respectively. Effect of diabetes: The relative increase in the retinal availability in the case of albino ipsilateral retina (686 ± 36) and vitreous (508 ± 43) was approximately 1.5–fold compared to the healthy animals. For the pigmented rats, the relative increase in the retinal (380 ± 33) and vitreal (138 ± 12) availability was approximately 2–fold.
Both the eye pigmentation and diabetic state influenced the retinal drug availability following subconjunctival injections. The retinal and vitreal drug availability was significantly lower for pigmented rats compared to the albino rats. The induction of diabetes increased the retinal and vitreal drug availability with the enhancement being greater in the pigmented rats compared to the albino rats.
This PDF is available to Subscribers Only