Eye / Vision
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/29926
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Browsing Eye / Vision by Author "Beall, Kallen"
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Item Endothelin B (ETB) receptor selective agonist endothelin 3 (ET-3) andmediated RGC death and implication for glaucoma.(2020) Kodati, Bindu; Krishnamoorthy, Raghu; Stankowska, Dorota; Harris, Payton; Wisniewski, Zoe; Krishnamoorthy, Vignesh; Beall, KallenPurpose: To determine if dietary administration of the dual ETA/ ETB receptor antagonist, macitentan, could protect retinal ganglion cells (RGCs) from cell death following an intravitreal injection of endothelin-1 (ET-1) and endothelin-3 (ET-3) in Brown Norway rats. Methods: Brown Norway rats (n=3 per group) were either untreated or treated with macitentan (5 mg/kg body weight) once a day for 3 days, followed by intravitreal injection of either 4 µl of 500 µM ET-1, ET-3 (2 nmole/eye) or vehicle in one eye. Following the injections, treatments with either macitentan or control gels without macitentan was continued for 7 days. After the treatments, retinal flat mounts were prepared and surviving RGCs were counted in a masked manner. Results: ET-1 produced 46% increase in RGC loss (p< 0.0001), compared to contralateral control eyes in rats 7 days post intravitreal administration. Macitentan treatment modestly protected from RGC loss following intravitreal ET-1 injection (27% RGC loss). ET-3 administration caused a modest increase (23%) in RGC death in this acute model, however, macitentan did not cause any further improvement in RGC survival (25% RGC loss). Conclusion: Both ET-1 and ET-3 mediate RGC loss following intravitreal administration in rats. Endothelin receptor antagonists have the potential to be developed as neuroprotective agents for the treatment of glaucoma.Item Novel Peptain for Neuroprotection in Glaucoma(2020) Stankowska, Dorota; Krishnamoorthy, Vignesh; Krishnamoorthy, Raghu; Chaphalkar, Renuka; Nagaraj, Ram; Nahomi, Rooban; Nam, Mi-hyun; Beall, Kallen; Brodrick, Ashley; Kodati, BinduPurpose: To determine if intravitreal administration of the core peptide of [alpha]-B crystallin, peptain-1 (P1) conjugated to a cell permeable peptide (CPP) (named P1-CPP) could inhibit retinal ganglion cell (RGC) death and functional decline in a rodent model of glaucoma. Methods: Primary RGCs were treated with endothelin-3 (ET-3) in the presence of either P1-CPP (12.5 µg/ml) or vehicle, following which RGC survival was assessed. In a different set of experiments, intraocular pressure (IOP) was elevated in one eye of Brown Norway (BN) rats and intravitreally injected with 2 µl of either P1-CPP or vehicle, once in a week for 6 weeks. RGC function was assessed by the pattern electroretinogram (PERG) amplitude. Retinal flat mounts were imaged and surviving RGCs were counted. Results: ET-3 treatment lead to 24% of RGCs loss compared to vehicle treated cells (p< 0.0001). P1-CPP treatment significantly lowered the ET-3-mediated cell loss (7% cell death, p< 0.001). IOP elevation in vehicle injected animals produced 11% and 27% loss of RGCs, in central and peripheral retina respectively, which was significantly lower in P1-CPP treated rats (7% loss in both eccentricities, **p< 0.01). P1-CPP treatment also promoted axonal protection during IOP elevation. IOP elevation caused 63% decline in the PERG amplitude (*p< 0.03) in comparison with naïve rats, which was sustained by P1-CPP treatment. Conclusion:The intravitreally injected P1-CPP provides cellular as well as functional protection of RGCs, which could facilitate neuroprotection against glaucomatous insults.