ABSTRACT
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.
Subject(s)
Fetal Tissue Transplantation/methods , Recovery of Function , Retina/transplantation , Retinal Degeneration/surgery , Visual Acuity , Animals , Disease Models, Animal , Electrophysiology , Electroretinography , Female , Immunohistochemistry , Male , Rats , Rats, Long-Evans , Rats, Nude , Retina/embryology , Retina/physiopathology , Retinal Degeneration/pathology , Retinal Degeneration/physiopathology , Tissue Donors , Tomography, Optical CoherenceABSTRACT
Reductions in the levels of the neuropeptide vasopressin (VP) and its receptors have been associated with schizophrenia. VP is also critical for appropriate social behaviors in humans as well as rodents. One of the prominent symptoms of schizophrenia is asociality and these symptoms may develop prodromally. A reduction in event-related potential (ERP) peak amplitudes is an endophenotype of schizophrenia. In this study, we use the Brattleboro (BRAT) rat to assess the role of VP deficiency in vocal communication during early development and on auditory ERPs during adulthood. BRAT rats had similar vocal communication to wild-type littermate controls during postnatal days 2 and 5 but the time between vocalizations was increased and the power of the vocalizations was reduced beginning at postnatal day 9. During adulthood, BRAT rats had deficits in auditory ERPs including reduced N40 amplitude and reduced low and high gamma intertrial coherence. These results suggest that the role of VP on vocal communication is an age-dependent process. Additionally, the deficits in ERPs indicate an impairment of auditory information processing related to the reduction in VP. Therefore, manipulation of the VP system could provide a novel mechanism for treatment for negative symptoms of schizophrenia.
