Safety of intravitreally administered recombinant erythropoietin (an AOS thesis).
OBJECTIVE
This study investigated the safety and potential retinal toxicity of intravitreally administered erythropoietin (EPO) in a rodent animal model.


METHODS
Forty-two healthy Sprague-Dawley rats were divided into one of 7 groups (N = 6 per group): control, sham injection, vehicle injection, and EPO injections of 50 ng (5 U), 100 ng (10 U), 250 ng (25 U), and 625 ng (62.5 U). Only the right eye was treated in each animal. Standard full-field dark- and light-adapted electroretinography (ERG) was obtained at 1 day prior to injection and then on postinjection days 3, 7, 14, and 21. Intraocular pressure (IOP) was measured at the conclusion of each ERG recording. Animals were sacrificed and the eyes underwent histologic examination with light microscopy and hematoxylin-eosin staining.


RESULTS
Rod peak, scotopic, and photopic responses (amplitude and latency) were not statistically different in the animals receiving 50 to 100 ng EPO. In the 250-ng group, the photopic b-wave amplitude at day 21 was elevated (P <.05), whereas in the 625-ng group, the scotopic OP3 latency ratio was higher at baseline (P <.05). No significant histologic abnormalities were noted except for one animal (625-ng group) with qualitative differences in retinal layer thickness and cellular density.


CONCLUSIONS
Intravitreal administration of EPO (at doses up to 625 ng) does not cause adverse effects on retinal function as assessed by ERG. Moreover, single intravitreal dosing does not appear to elicit retinal neovascularization. Further investigation is warranted to assess fully the potential of this neuroprotective cytokine as a treatment for glaucoma.
Tsai
James C
JC
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, Connecticut, USA.
D000818:Animals; D004596:Electroretinography / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000633:toxicity*; D007267:Injections; D007429:Intraocular Pressure; D008297:Male; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects; D014822:Vitreous Body
D011994:Recombinant Proteins; D004921:Erythropoietin