Abstract
Purpose: :
Inherited retinal degenerations are characteristic of retinal neuronal apoptosis and retinal vasculature apoptosis. While retinal vascular apoptosis is thought to be followed by the diminished metabolic demand due to the retinal degeneration, the precise relation between the retinal neuronal and vascular degeneration is not well understood. Endothelial progenitor cells (EPCs) circulate in the blood and respond to tissue ischemia and contribute to angiogenesis. Recently, EPCs come into clinical use for several cardiovascular diseases. We previously reported that EPCs with low activity of aldehyde dehydrogenase (Alde) possess a greater ability for repairing ischemic tissue than Alde-High EPCs. To evaluate the effect of Alde-Low EPCs for vascular attenuation disease, Alde-Low and -High EPCs were injected into eye with rd1 model mouse of retinal degeneration.
Methods: :
Alde-Low and -High EPCs, HUVEC, and PBS were injected intravitrealy and subretinaly of a P6 mouse. The vascular length of deep layer and the number of rows were analyzed by histologically and immunohistochemistry. Apoptosis were evaluated by TUNEL analysis.
Results: :
The photoreceptors containing the outer nuclear layer (ONL) rapidly degenerates by postnatal day 20 (P20) due to apoptosis. Mouse retina is consisted of three vasculature layers; surface, intermediate, and deep layer. The vasculatures of deep layer almost disappear by P21. Intravitreal injection of Alde-Low EPCs rescued the degeneration of vascular and neural cells. And the vascular length of deep layer and the number of rows in ONL were greater in Alde-Low EPC injection compared to the injection of Alde-High EPC, HUVEC, and PBS (p<0.01). Alde-Low EPCs also decreased the number of apoptotic cells in ONL. Subretinal injection of Alde-Low EPCs showed greater rescued effect than intravitreal injection.
Conclusions: :
Injection of Alde-Low EPCs may have suppressive effect for degeneration of vascular and neural cells in rd1 mice.
Keywords: retinal degenerations: cell biology • regeneration • injection