Phenotype Characterization of a Mice Genetic Model of Absolute Blindness

Abstract

Recent technological development requires new approaches to address the problem of blindness. Such approaches need to be able to ensure that no cells with photosensitive capability remain in the retina. The presented model, Opn4−/− × Pde6brd10/rd10 (O×Rd) double mutant murine, is a combination of a mutation in the Pde6b gene (photoreceptor degeneration) together with a deletion of the Opn4 gene (responsible for the expression of melanopsin in the intrinsically photosensitive retinal ganglion cells). This model has been characterized and compared with those of WT mice and murine animal models displaying both mutations separately. A total loss of pupillary reflex was observed. Likewise, behavioral tests demonstrated loss of rejection to illuminated spaces and a complete decrease in visual acuity (optomotor test). Functional recordings showed an absolute disappearance of various wave components of the full-field and pattern electroretinogram (fERG, pERG). Likewise, visual evoked potential (VEP) could not be recorded. Immunohistochemical staining showed marked degeneration of the outer retinal layers and the absence of melanopsin staining. The combination of both mutations has generated an animal model that does not show any photosensitive element in its retina. This model is a potential tool for the study of new ophthalmological approaches such as optosensitive agents.

Oxidative Model of Retinal Neurodegeneration Induced by Sodium Iodate: Morphofunctional Assessment of the Visual Pathway

“…This test measures the visual acuity of the animals by observing the movement of the animal’s eyes/head following the direction of rotation of the grating stimuli [ 40 ]. The spatial frequency, direction, and contrast of the stimuli were varied to determine visual acuity.…”

“…This test measures the pupillary contraction of the animals to a light stimulus [ 40 ]. It was observed that NaIO 3 injection significantly decreased pupillary contraction, manifesting as a smaller change in the pupillary area to three consecutive stimuli (see Figure 3 ).…”

“…This reflex starts with the involvement of photoreceptors and melanopsin ganglion cells [ 49 ]. Since the mice used in this model had a mutation in the melanopsin gene ( Opn4 −/− ) that canceled its photosensitive function, the responses obtained in this reflex after the injection of sodium iodate corresponded exclusively to the photoreceptors, and their decrease was a faithful reflection of the lesion they suffered [ 40 ]. The novelty of these experiments is that their results reinforce the correlation with pupillary reflex dysfunction observed in patients suffering from various retinal disorders [ 50 , 51 , 52 , 53 ].…”

Piceid Octanoate Protects Retinal Cells against Oxidative Damage by Regulating the Sirtuin 1/Poly-ADP-Ribose Polymerase 1 Axis In Vitro and in rd10 Mice

“…Under normal conditions, wildtype mice tend to stay longer in the dark area since their exploratory behavior toward a new environment is suppressed by the negative stimulus produced by the illuminated area. In the case of rd10 mice, it has been described that the time they remained in the dark chamber was longer, and the rejection of the illuminated compartment increased when light intensity was higher [104]. This aversion to the light of rd10 has been explained by the persistence of photosensitive elements within the degenerative retinas of rd10 mice [104].…”

“…In the case of rd10 mice, it has been described that the time they remained in the dark chamber was longer, and the rejection of the illuminated compartment increased when light intensity was higher [104]. This aversion to the light of rd10 has been explained by the persistence of photosensitive elements within the degenerative retinas of rd10 mice [104]. PIC-OCTtreated mice spent more time in the illuminated chamber than untreated ones, who showed rejection of the illuminated compartment, with less access and time spent in the light chamber.…”