Browsing by Subject "Rabbits"
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Item Effect of Cromakalim Prodrug 1 (CKLP1) on Aqueous Humor Dynamics and Feasibility of Combination Therapy With Existing Ocular Hypotensive Agents(ARVO Journals, 2017-11-01) Roy Chowdhury, Uttio; Rinkoski, Tommy A.; Bahler, Cindy K.; Millar, J. Cameron; Bertrand, Jacques A.; Holman, Bradley H.; Sherwood, Joseph M.; Overby, Darryl R.; Stoltz, Kristen L.; Dosa, Peter I.; Fautsch, Michael P.Purpose: Cromakalim prodrug 1 (CKLP1) is a water-soluble ATP-sensitive potassium channel opener that has shown ocular hypotensive properties in ex vivo and in vivo experimental models. To determine its mechanism of action, we assessed the effect of CKLP1 on aqueous humor dynamics and in combination therapy with existing ocular hypotensive agents. Methods: Outflow facility was assessed in C57BL/6 mice by ex vivo eye perfusions and by in vivo constant flow infusion following CKLP1 treatment. Human anterior segments with no trabecular meshwork were evaluated for effect on pressure following CKLP1 treatment. CKLP1 alone and in combination with latanoprost, timolol, and Rho kinase inhibitor Y27632 were evaluated for effect on intraocular pressure in C57BL/6 mice and Dutch-belted pigmented rabbits. Results: CKLP1 lowered episcleral venous pressure (control: 8.9 +/- 0.1 mm Hg versus treated: 6.2 +/- 0.1 mm Hg, P < 0.0001) but had no detectable effect on outflow facility, aqueous humor flow rate, or uveoscleral outflow. Treatment with CKLP1 in human anterior segments without the trabecular meshwork resulted in a 50% +/- 9% decrease in pressure, suggesting an effect on the distal portion of the conventional outflow pathway. CKLP1 worked additively with latanoprost, timolol, and Y27632 to lower IOP, presumably owing to combined effects on different aspects of aqueous humor dynamics. Conclusions: CKLP1 lowered intraocular pressure by reducing episcleral venous pressure and lowering distal outflow resistance in the conventional outflow pathway. Owing to this unique mechanism of action, CKLP1 works in an additive manner to lower intraocular pressure with latanoprost, timolol, and Rho kinase inhibitor Y27632.Item Topical Estrogen Therapy for Hyperopia Correction in Vivo(ARVO Journals, 2020-06-03) Leshno, Ari; Prokai-Tatrai, Katalin; Rotenstreich, Ygal; Magid, Asaf; Bubis, Ettel; Schwartz, Shulamit; Skaat, Alon; Zloto, Ofira; Avni-Zauberman, Noa; Barak, AdielPurpose: In vitro studies found that 17beta-estradiol (estrogen) modulates corneal biomechanical properties and reduces tissue stiffness. Therefore we hypothesized that topical estrogen might affect the refractive properties of the cornea, inducing a myopic shift. Methods: Twelve female New Zealand white rabbits 16 weeks old were used. The rabbits were randomly divided to either the treatment group receiving 1.5% (w/v) estrogen eye drops or a control group receiving vehicle only (n = 6 each group). Both groups were given drops (50 microL) to the right eye every 12 hours for 35 days. Ocular examination, pachymetry, intraocular pressure (IOP), keratometry ,and refraction were evaluated at baseline and on a weekly basis. Results: No significant differences were observed between the two groups at baseline in all outcome measures. Both groups displayed corneal flattening and a hyperopic shift. However, the change rate was slower in the treatment group. Repeated measurements analysis revealed a statistically significant difference in keratometry readings between groups (P = 0.034) with steeper keratometry by up to 0.6 diopters in the treatment group. The difference between the two groups diminished and became statistically insignificant after treatment cessation. No significant changes were observed in IOP and pachymetry throughout the study period. No side effects were observed in either group. Conclusions: Estrogen eye drops induced a myopic shift in keratometry readings. These results suggest that corneal refractive power might be manipulated pharmacologically. Further studies on the physiology behind this change are warranted to facilitate a pathway for development of novel pharmacologic treatments to correct refractive errors.