Michael M. Lai

Fate of Embryonic Stem Cell Derivatives Implanted into the Vitreous of a Slow Retinal Degenerative Mouse Model

Stem cell therapy may be used potentially to treat retinal degeneration and restore vision. Since embryonic stem cells (ESCs) can differentiate into almost any cell types, including those found in the eye, they can be transplanted to repair or replace damaged or injured retinal tissue resulting from inherited diseases or traumas. In this investigation, we explored the potential of ESCs and ESC-derived neuroprogenitors to proliferate and integrate into the diseased retinal tissue of rd12 mice. These rd12 mice mimic the slow and progressive retinal degeneration seen in humans. Both ESCs and ESC-derived neuroprogenitors from ESCs survived and proliferated as evidenced from an increase in yellow fluorescent protein fluorescence. Quantification analysis of cryosectioned retinal tissue initially revealed that both ESCs and neuroprogenitors differentiated into cells expressing neural markers. However, ESC proliferation was robust and resulted in the disruption of the retinal structure and the eventual formation of teratomas beyond 6 weeks postimplantation. In contrast, the neuroprogenitors proliferated slowly, but differentiated further and integrated into the retinal layers of the eye. The differentiation of neuroprogenitors represented various retinal cell types, as judged from the expression of cell-specific markers including Nestin, Olig1, and glial fibrillary acidic protein. These results suggest that ESC-derived neuroprogenitors can survive, proliferate, and differentiate when implanted into the eyes of experimental mice and may be used potentially as cell therapy for treating degenerated or damaged retinal tissue.

Treatment of vascularly active familial exudative vitreoretinopathy with pegaptanib sodium (Macugen).

Purpose: To report results of treatment of vascularly active familial exudative vitreoretinopathy (FEVR) with pegaptanib sodium (Macugen; Eyetech Pharmaceuticals, New York, NY) injection. Methods: In a retrospective case series, four patients with vascularly active FEVR, as demonstrated by increasing subretinal exudation despite photocoagulation, cryotherapy, and/or intravitreal steroid injection, received a single intravitreal injection of pegaptanib sodium. Preinjection and postinjection fundus photography, fluorescein angiography, and optical coherence tomography were performed to evaluate the changes in visual acuity, vascular activity, and amount of exudation. Results: The mean follow-up period was 11.2 months (range, 8.1–15.5 months) after the first intravitreal injection. All four patients had a decrease in exudation after treatment with pegaptanib sodium documented by a decrease in subretinal exudate by fundus photography and decreased leakage by fluorescein angiography. After reduction of exudation, two patients required vitrectomy to relieve vitreoretinal traction. Visual acuity improved in two patients, stabilized in one patient, and worsened in one patient secondary to tractional retinal detachment. No injection-associated systemic or ocular complications were observed in any of the treated patients. Conclusions: Intravitreal injection of pegaptanib sodium is a potential treatment option for patients with FEVR and worsening exudation despite treatment with standard therapy. Vitreoretinal traction may develop with rapid resolution of subretinal exudates, requiring surgical intervention. However, visual acuity can improve after retinal traction is released. Further studies using anti-vascular endothelial growth factor agents are needed to better understand treatment of FEVR.

Septo-optic dysplasia associated with abnormal foveal development.

PURPOSE To report a case of abnormal foveal development in a patient with septo-optic dysplasia. METHODS Observational case report, consisting of clinical examination, fluorescein angiography, and optical coherence tomographic (OCT) evaluation of a patient who presented with septo-optic dysplasia. RESULTS A 3-month-old girl with septo-optic dysplasia was found to have bilateral foveal schisis by OCT and absence of foveal avascular zone by fluorescein angiography. CONCLUSIONS Abnormal foveal development can be seen in patients with septo-optic dysplasia. Both foveal schisis and absence of foveal avascular zone may contribute to visual outcome. Detailed macular evaluation is recommended in patients who present with optic nerve hypoplasia.