Abstract
Purpose :
Novel therapeutic agents derived from biological molecules and stem cells are of interest for treatment of retinal degenerations and injuries. Effective delivery methods for these agents must enhance their ocular transport and pharmacokinetics, as well as survival in the host environment. Hydrogels are proven delivery vehicles for cells; as a case study, we examined the intraocular toxicity of HyStem™, a hyaluronic acid polymer, in the eyes of normal rabbits to assess its effect on the functional and morphological status of the eye.
Methods :
Experiments were carried out in six rabbits: three Dutch Belted and three NZ pigmented animals (RSI, Mockville, NC). The Hystem hydrogel was conjugated with fluorescein to determine its location in the eye by fluorescence photography. In each animal, 10 µl of hydrogel was injected into one eye, while 10 µl of BSS (the vehicle) was injected into the fellow eye. The status of the eye was followed for six weeks with fundus photos, optical coherence tomography (OCT), and flash & flicker electroretinography (ERG), compared to pre-injection examinations.
Results :
One-hr post-hydrogel injection, fluorescence photography revealed a diffuse emission from the fundus, suggesting a general dispersion of the hydrogel, rather than a discrete accumulation on the retina. The fundus appearance itself was normal. Weak fluorescence remained at 1-wk post-injection, becoming unobservable at later time points. The OCT imaging did not show abnormalities or thickening of the retina indicative of edema or an inflammatory response (mean±std of treated eyes: 226.1±9.46 µm, control eyes: 232.49±13.8 µm). Flash and flicker ERG recordings of the eyes were stable over the six-week follow-up, and the mean b-wave amplitudes of the treated eyes (104.8±24.0 µV) and control eyes (109.8±23.41 µV) did not differ significantly (p>0.05, t-test). At the six-week follow-up time point, the animals were euthanized and the eyes harvested for histological examination.
Conclusions :
Injection of Hystem™ hydrogel into the rabbit eye was tolerated well by the host. Over a six-week period, the eyes’ retinas by fundus photography and OCT remained normal, and the visual function as assessed by photopic ERG was stable. Histological examinations of the retinas were unremarkable. Both rabbit strains reacted similarly to the hydrogel injection, and were equally suitable for this type of experimental program.
This is a 2020 ARVO Annual Meeting abstract.