Neuroprotection of photoreceptors by direct delivery of erythropoietin to the retina of the retinal degeneration slow mouse.
The primary objectives of this study were to determine if erythropoietin (EPO) is neuroprotective to the photoreceptors in the retinal degeneration slow (rds) mouse in the absence of an increase in hematocrit and to determine if deglycosylated EPO (DEPO) is less neuroprotective. We performed subretinal injections of 10U EPO, DEPO or hyperglycosylated EPO (HEPO) in postnatal day 7 rds mice. Whole eye EPO levels were quantified by ELISA at specified time points post-injection. TUNEL analysis, hematocrit, and immunohistochemistry were performed at postnatal day 20. Half of the amount of EPO measured immediately after injection was detected less than 1 h later. Twenty four hours later, EPO levels were 1000 times lower than the amount originally detected. Uninjected rds mice contained 36 +/- 2 TUNEL-positive cells/mm retina and PBS injected mice contained 17 +/- 3 TUNEL-positive cells/mm retina. EPO, DEPO, and HEPO treated rds retinas contained 5 +/- 2, 9 +/- 2, and 3 +/- 1 TUNEL-positive cells/mm retina, respectively. The hematocrit was 43% in control and 41% in treated rds mice Previous studies have shown neuroprotection of the retina by treatment with as little as 24-39 mU EPO/mg total protein in the eye. In this study, we detected 40 mU/mg EPO in the eye 11 h after injection of 10 U EPO. Treatment with all forms of EPO tested was neuroprotective to the photoreceptors without a concomitant increase in hematocrit.
Rex
Tonia S
TS
The Hamilton Eye Institute, Department of Ophthalmology, The University of Tennessee Health Science Center, 930 Madison Ave., Ste 731, Memphis, TN 38163, USA. trex@utmem.edu
Wong
Ying
Y
Kodali
Kishore
K
Merry
Shayla
S
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D000068256:Darbepoetin alfa; D000229:Dependovirus / Q000235:genetics; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006031:Glycosylation; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006400:Hematocrit; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007267:Injections; D007381:Intermediate Filament Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D064531:Peripherins; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011499:Protein Processing, Post-Translational; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014161:Transduction, Genetic
D007381:Intermediate Filament Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D064531:Peripherins; C578996:Prph2 protein, mouse; C485184:enhanced green fluorescent protein; D004921:Erythropoietin; D049452:Green Fluorescent Proteins; D000068256:Darbepoetin alfa