Abstract
Purpose: :
To study the effect of embryonic stem cells administered by intravitreal injection on the murine model of hyperoxia-related retinal degeneration (HRRD).
Methods: :
C57BL/6J mice were studied using hyperoxic conditions described by Yamada et al. {Smit-McBride, 2007}. Briefly, they were exposed to 70% oxygen for 14 days. Under these conditions, these mice are known to develop a regional retinal degeneration affecting the outer nuclear layer. Using this model, we administered GFP-expressing cells from the 129 background into the vitreous at day 3 of the hyperoxic conditions. Outer nuclear layer (ONL) thickness was measured and retinal histology was studied at various time points after removal from the hyperoxic chambers. Embryonic stem cells were identified by GFP expression.
Results: :
Regional retinal degeneration was demonstrated as previously described. Embryonic stem cells were delivered efficiently by intravitreal injection, and they appear to remain viable in the vitreous even at the later time points. The majority of the mice did not form teratomas. The embryonic stem cells appear to largely remain in the vitreous cavity or on the surface of the internal limiting membrane of the retina. Few GFP+ cells (embryonic cells) were found within the host retina in this model despite the localized retinal degeneration. Furthermore, the presence of the embryonic stem cells appeared to have limited influence on the amount of ONL degeneration. Additional studies are ongoing to determine if there are subtle trends in the amount of ONL cell loss.
Conclusions: :
Embryonic stem cells can be delivered to the vitreous and survive in this model of retinal degeneration. Embryonic stem cells from the 129 background have limited migration in HRRD. They mostly stay within the vitreous without crossing the internal limiting membrane of the retina. Furthermore, they have limited effect on the degree of retinal degeneration of the outer nuclear layer. Additional studies are needed to determine factors to influence embryonic stem cell migration from the vitreous in this model of hyperoxia-induced regional retinal degeneration.
Keywords: retina • oxidation/oxidative or free radical damage • age-related macular degeneration