Organization of the retina of the CRX (-/-) mouse: Structural changes and Cannabinoid expression

Michael Wennervaldt Jørgensen

Student thesis: Master thesis

Abstract

The Cone-rod homebox (CRX) gene is vital for normal retinal photoreceptor development and maintenance. Lack of a functional CRX gene leads to the absence of the outer segments (OS) in photoreceptor cells and thus congenitally blindness (Furukawa et al. 1999). Mutations in the CRX gene have been associated with the photoreceptor degenerative retinopathies Leber Congenital Amaurosis (LCA), Retinitis Pigmentosa and Cone-Rod Dystrophy (Tran et al. 2014). Additionally, recent studies have shown the presence and function of the endocannabinoid system in the retina and visual system (Ptito, Casanova, and Bouchard 2016). In this immunohistochemical study of the CRX-/- mouse retina we confirmed the lack of photoreceptor outer segment. We found that the retinal organization is affected by the pathology. The CRX-/- retina is overall thinner and the outer nuclear layer and ganglion cell layer (GCL) is diminished. The displaced amacrine cells are absent and only a few calbindin positive amacrine cells were observed. The nucleus of some bipolar cells was displaced to the inner plexiform layer and the outer nuclear layer. We assessed the expression of CB1 expression to only be localized in the GCL of CRX-/-, whereas it was expressed throughout the retinal layers in control. Moreover, we found melanopsin positive cells in the GCL, albeit with abnormal morphology, suggesting functional retinal activity in the GCL despite congenitally blind. Furthermore, the presence of melanopsin positive cells suggests functional non-image forming system in the CRX-/-, which is augmented by a normal circadian rhythm (Furukawa et al. 1999). These preliminary observations indicate potentiality in the CRX-/- mouse as model for further investigations in the endocannabinoid system and the non-image forming system of the congenitally blind.

EducationsPharmaceutical Biology, (Bachelor/Graduate Programme) Graduate
LanguageEnglish
Publication dateJun 2016
Number of pages60
SupervisorsLouise Torp Dalgaard & Maurice Ptito