Abstract:Dysfunction of the key sense of vision, leading to visual handicap or blindness, has a crucial effect on day‐to‐day life. In this commentary, I will summarize the work in my laboratory that is focused on a basic understanding of visual processing and the use of this information to understand disease mechanism and to develop correcting therapies. We are beginning to understand how cell types of the visual system interact in local circuits and compute visual information. This has brought insight into mechanisms … Show more
“…This disrupts axogenesis, dendritogenesis, and neuronal guidance in brain areas involved in the control of eye movement ( 30 ). FRMD7 promoted neurite elongation by modulating actin cytoskeleton whereas FRMD7 gene knockdown led to a significant reduction in overall neurite length ( 34 , 38 ), further contributing to the development of neuronal circuit asymmetry and neurological disorders ( 28 , 39 ). Mutations associated with ICN include missense mutations, null mutations, deletions and insertions, and frameshift mutations.…”
BackgroundIdiopathic congenital nystagmus (ICN) is an inherited disorder characterized by uncontrollable binocular conjugating oscillation. X-linked idiopathic congenital nystagmus is one of the most prevalent types of ICN. Elucidation of the genetic mechanisms involved in ICN will enhance our understanding of its molecular etiology.Case presentationWe report a girl with uncontrollable binocular oscillation and anomalous head posture, then presented a novel heterozygous missense variant (c.686G>T) within the mutation-rich region of the FERM domain containing 7 (FRMD7) gene in her family member. The girl received occlusion therapy and surgical operation which balanced her binocular vision and corrected the anomalous head posture.ConclusionsThis is the first report on a mutation (c.686G>T) caused the substitution of Arg (R) with Leu (L) at position 229 (p.R229L) of the FRMD7 protein in a patient with ICN.
“…This disrupts axogenesis, dendritogenesis, and neuronal guidance in brain areas involved in the control of eye movement ( 30 ). FRMD7 promoted neurite elongation by modulating actin cytoskeleton whereas FRMD7 gene knockdown led to a significant reduction in overall neurite length ( 34 , 38 ), further contributing to the development of neuronal circuit asymmetry and neurological disorders ( 28 , 39 ). Mutations associated with ICN include missense mutations, null mutations, deletions and insertions, and frameshift mutations.…”
BackgroundIdiopathic congenital nystagmus (ICN) is an inherited disorder characterized by uncontrollable binocular conjugating oscillation. X-linked idiopathic congenital nystagmus is one of the most prevalent types of ICN. Elucidation of the genetic mechanisms involved in ICN will enhance our understanding of its molecular etiology.Case presentationWe report a girl with uncontrollable binocular oscillation and anomalous head posture, then presented a novel heterozygous missense variant (c.686G>T) within the mutation-rich region of the FERM domain containing 7 (FRMD7) gene in her family member. The girl received occlusion therapy and surgical operation which balanced her binocular vision and corrected the anomalous head posture.ConclusionsThis is the first report on a mutation (c.686G>T) caused the substitution of Arg (R) with Leu (L) at position 229 (p.R229L) of the FRMD7 protein in a patient with ICN.
“…Similarly, an AAV viral capsid that penetrates the primate retina (Byrne et al, 2020) and could be developed for use in human gene transfer experiments was identified. Several excellent reviews describe other aspects of gene therapy in the eye (Cideciyan and Jacobson, 2019;Roska, 2019;Roska and Sahel, 2018).…”
Section: Genetic Methods To Rescue Visionmentioning
confidence: 99%
“…Similarly, an AAV viral capsid that penetrates the primate retina ( 155 ) and could be developed for use in human gene transfer experiments was identified. Several excellent reviews describe other aspects of gene therapy in the eye ( 12 , 156 , 157 ). Figure 5 Pharmacological intervention using genetic methods.…”
Section: Genetic Methods To Rescue Visionmentioning
All that we view of the world begins with an ultrafast cis to trans photoisomerization of the retinylidene chromophore associated with the visual pigments of rod and cone photoreceptors. The continual responsiveness of these photoreceptors is then sustained by regeneration processes that convert the trans- retinoid back to an 11-cis configuration. Recent biochemical and electrophysiological analyses of the retinal G protein-coupled receptor (RGR) suggest that it could sustain the responsiveness of photoreceptor cells, particularly cones, even under bright light conditions. Thus, two mechanisms have evolved to accomplish the re-isomerization: one involving the well-studied retinoid isomerase (RPE65), and a second photoisomerase reaction mediated by the RGR. Impairments to the pathways that transform all- trans-retinal back to 11-cis-retinal are associated with mild to severe forms of retinal dystrophy. Moreover, with age there also is a decline in the rate of chromophore regeneration. Both pharmacological and genetic approaches are being used to bypass visual cycle defects and consequently mitigate blinding diseases. Rapid progress in the use of genome editing also is paving the way for the treatment of disparate retinal diseases. In this review, we provide an update on visual cycle biochemistry and then discuss visual cycle-related diseases and emerging therapeutics for these disorders. There is hope that these advances will be helpful in treating more complex diseases of the eye, including age-related macular degeneration (AMD).
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