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1.
Invest Ophthalmol Vis Sci ; 58(1): 614-630, 2017 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-28129425

RESUMEN

Purpose: To characterize a recently developed model, the retinal degenerate immunodeficient S334ter line-3 rat (SD-Foxn1 Tg(S334ter)3Lav) (RD nude rat), and to test whether transplanted rat fetal retinal sheets can elicit lost responses to light. Methods: National Institutes of Health nude rats (SD-Foxn1 Tg) with normal retina were compared to RD nude rats with and without transplant for morphology and visual function. Retinal sheets from transgenic rats expressing human placental alkaline phosphatase (hPAP) were transplanted into the subretinal space of RD nude rats between postnatal day (P) 26 and P38. Transplant morphology was examined in vivo using optical coherence tomography (OCT). Visual function was assessed by optokinetic (OKN) testing, electroretinogram (ERG), and superior colliculus (SC) electrophysiology. Cryostat sections were analyzed for various retinal/synaptic markers and for the expression of donor hPAP. Results: Optical coherence tomography scans showed the placement and laminar development of retinal sheet transplants in the subretinal space. Optokinetic testing demonstrated a deficit in visual acuity in RD nude rats that was improved after retinal sheet transplantation. No ERG responses were detected in the RD nude rats with or without transplantation. Superior colliculus responses were absent in age-matched control and sham surgery RD nude rats; however, robust light-evoked responses were observed in a specific location in the SC of transplanted RD nude rats. Responsive regions corresponded to the area of transplant placement in the eye. The quality of visual responses correlated with transplant organization and placement. Conclusions: The data suggest that retinal sheet transplants integrate into the host retina of RD nude rats and recover significant visual function.


Asunto(s)
Trasplante de Tejido Fetal/métodos , Recuperación de la Función , Retina/trasplante , Degeneración Retiniana/cirugía , Agudeza Visual , Animales , Modelos Animales de Enfermedad , Electrofisiología , Electrorretinografía , Femenino , Inmunohistoquímica , Masculino , Ratas , Ratas Long-Evans , Ratas Desnudas , Retina/embriología , Retina/fisiopatología , Degeneración Retiniana/patología , Degeneración Retiniana/fisiopatología , Donantes de Tejidos , Tomografía de Coherencia Óptica
2.
Exp Eye Res ; 91(5): 727-38, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20804751

RESUMEN

The aim of this study was to compare glial-derived neurotrophic factor (GDNF) treatment with brain-derived neurotrophic factor (BDNF) treatment of retinal transplants on restoration of visual responses in the superior colliculus (SC) of the S334ter line 3 rat model of rapid retinal degeneration (RD). RD rats (age 4-6 weeks) received subretinal transplants of intact sheets of fetal retina expressing the marker human placental alkaline phosphatase (hPAP). Experimental groups included: (1) untreated retinal sheet transplants, (2) GDNF-treated transplants, (3) BDNF-treated transplants, (4) none surgical, age-matched RD rats, (5) sham surgery RD controls, (6) progenitor cortex transplant RD controls, and (7) normal pigmented rat controls. At 2-8 months after transplantation, multi-unit visual responses were recorded from the SC using a 40 ms full-field stimulus (-5.9 to +1 log cd/m(2)) after overnight dark-adaptation. Responses were analyzed for light thresholds, spike counts, response latencies, and location within the SC. Transplants were grouped into laminated or rosetted (more disorganized) transplants based on histological analysis. Visual stimulation of control RD rats evoked no responses. In RD rats with retinal transplants, a small area of the SC corresponding to the position of the transplant in the host retina, responded to light stimulation between -4.5 and -0.08 log cd/m(2), whereas the light threshold of normal rats was at or below -5 log cd/m(2) all over the SC. Overall, responses in the SC in rats with laminated transplants had lower response thresholds and were distributed over a wider area than rats with rosetted transplants. BDNF treatment improved responses (spike counts, light thresholds and responsive areas) of rats with laminated transplants whereas GDNF treatment improved responses from rats with both laminated and rosetted (more disorganized) transplants. In conclusion, treatment of retinal transplants with GDNF and BDNF improved the restoration of visual responses in RD rats; and GDNF appears to exert greater overall restoration than BDNF.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/farmacología , Trasplante de Tejido Fetal , Factor Neurotrófico Derivado de la Línea Celular Glial/farmacología , Retina/fisiología , Retina/trasplante , Degeneración Retiniana/cirugía , Animales , Animales Modificados Genéticamente , Electrofisiología , Potenciales Evocados Visuales/fisiología , Femenino , Masculino , Microesferas , Estimulación Luminosa , Ratas , Retina/citología , Degeneración Retiniana/fisiopatología , Células Madre/efectos de los fármacos , Colículos Superiores/fisiología
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