Postnatal Visual Deprivation in Rats Regulates Several Retinal Genes and Proteins, Including Differentiation-Associated Fibroblast Growth Factor-2

Abstract

Little is known about the retinal cellular basis of amblyopia, which is a developmental disease characterized by impaired visual acuity. This study examined the retinal transcripts associated with experimentally induced unilateral amblyopia in rats. Surgical tarsorrhaphy of the eyelids on one side was performed in pups prior to eye opening at postnatal day 14, thereby preventing any visual experience. This condition was maintained for over 2 months, after which electroretinograms (ERGs) were recorded, the retinal ganglion cell (RGC) arrangement and number were determined using neuroanatomical tracing, the retinal transcripts were studied using microarray analysis, regulated mRNAs were confirmed with quantitative reverse-transcriptase PCR, and proteins were stained using Western blotting and immunohistochemistry. An attenuated ERG was found in eyes that were deprived of visual experience. Retrograde neuroanatomical staining disclosed a larger number of RGCs within the retina on the visually deprived side compared to the non-deprived, control side, and a multilayered distribution of RGCs. At the retinomic level, several transcripts associated with retinal differentiation, such as fibroblast growth factor 2 (FGF-2), were either up- or downregulated. Most of the transcripts could be verified at the mRNA level. To unravel the role of a differentiation-associated protein, we tested FGF-2 in dissociated postnatal retinal cell cultures and found that FGF-2 is a potent factor triggering ganglion cell differentiation. The data suggest that visual experience shapes the postnatal retinal differentiation, whereas visual deprivation induces changes at the functional, cellular and molecular levels within the retina.

Evaluation of Retinal Nerve Fiber Layer Thickness and Macular Thickness in Amblyopic Children

“…Huynh et al and Pang et al also stated that the pause of normal postnatal changes and the interruption of the henle layer organization and foveal maturation may cause an increase in foveal thickness in amblyopia 39,40 . A recent study supported this hypothesis, demonstrating that the visual deprivation induced molecular, cellular and functional changes by affecting the postnatal differentiation in the retina 13 . This raises the question of whether there is a change in the macular and RNFL thickness after the treatment.…”

“…With the introduction of functional magnetic resonance imaging (MRI), morphological and functional deficits have been presented in the LGN, striate cortex and extrastriate cortex in the humans with amblyopia [7][8][9] . The changes occurring in the retina and optic nerve in the case of amblyopia have been researched from past to present, and there is no approved results have been reached so far [10][11][12][13] .…”

Expression and significance of miR - 20b in retinal photoreceptor cells exposed to PCB1254

“…FGF2-like molecules may be secreted by neighboring cells, such as the retinal pigment epithelium, and they are involved in retinal development and differentiation [20]. Recent studies have shown that FGF2 plays an important role in the treatment of neuroretinal degeneration, myopia, vitreous lesions and in the protection of photoreceptors from oxidative damage [21]. GRB2 is a cytoplasmic protein that contains the src-homology 3 (SH3) domain flanking two single SH2 domains and plays an important role in the coupling of receptor tyrosine kinases to downstream signaling [22].…”

Transplantation of Neuro2a Cells into the Developing Postnatal Mouse Eye

“…We investigated the protein expression of two growth factors in N2a cells in order to identify the direct factors targeting the differentiation of N2a cells treated with CM from the retinas of P5 mice. Among several secreted factors, we focused on TGFβ2 and FGF-2, which promote the survival and differentiation of retinal cells [ 4 , 12 , 22 , 32 ]. TGFβ2 signaling has a neuroprotective effect in the retina, modulates the cell death of progenitors during the development of the vertebrate retina and regulates retinal thickness [ 2 , 6 ].…”