Retinal TrkB receptors regulate neural development in the inner, but not outer, retina

Grishanin, Ruslan N.; Yang, Hongbo; Liu, Xiaorong; Donohue–Rolfe, K.M.; Nune, George; Zang, Keling; Xu, Baoji; Duncan, Jacque L.; LaVail, Matthew M.; Copenhagen, David R.; Reichardt, Louis F.

doi:10.1016/j.mcn.2008.04.004

Cited by 49 publications

(61 citation statements)

References 83 publications

(119 reference statements)

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“…Moreover, as its name indicates, Rai1 expression is induced by retinoic acid (Imai et al, 1995). Because retinoic acid signaling is a major pathway involved in eye formation (Cvekl and Wang, 2009) and other developmental processes, and because RAI1 appears to help assemble and maintain neuronal circuitry (Huang et al, 2016), the lack of one Rai1 allele is likely to impact eye development and light signaling pathways, maybe through its target gene Bdnf , which is known to be important for retinal development and synaptic connectivity (Grishanin et al, 2008). While we found no apparent structural differences in the retina, the ERG results did reveal a profound attenuation of the response to light pointing to altered retinal function.…”

Section: Discussionmentioning

confidence: 99%

Rai1 frees mice from the repression of active wake behaviors by light

Diessler

Kostic

Arsenijévic

et al. 2017

eLife

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Besides its role in vision, light impacts physiology and behavior through circadian and direct (aka ‘masking’) mechanisms. In Smith-Magenis syndrome (SMS), the dysregulation of both sleep-wake behavior and melatonin production strongly suggests impaired non-visual light perception. We discovered that mice haploinsufficient for the SMS causal gene, Retinoic acid induced-1 (Rai1), were hypersensitive to light such that light eliminated alert and active-wake behaviors, while leaving time-spent-awake unaffected. Moreover, variables pertaining to circadian rhythm entrainment were activated more strongly by light. At the input level, the activation of rod/cone and suprachiasmatic nuclei (SCN) by light was paradoxically greatly reduced, while the downstream activation of the ventral-subparaventricular zone (vSPVZ) was increased. The vSPVZ integrates retinal and SCN input and, when activated, suppresses locomotor activity, consistent with the behavioral hypersensitivity to light we observed. Our results implicate Rai1 as a novel and central player in processing non-visual light information, from input to behavioral output.DOI: http://dx.doi.org/10.7554/eLife.23292.001

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Section: Discussionmentioning

confidence: 99%

Rai1 frees mice from the repression of active wake behaviors by light

Diessler

Kostic

Arsenijévic

et al. 2017

eLife

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“…The finding of a variant in a neural growth factor was novel and also aligned with several current experimental and preclinical studies showing the importance of neurovascular interactions in retinal vascular development and ROP. [35][36][37][38][39][40] It was not ethically possible to enroll preterm infants in the replication cohort who were similar to those in the discovery cohort, because since the ETROP study ophthalmologists treat infants for ROP less severe than threshold disease. Infants enrolled in the replication cohort represented the mix seen in many studies.…”

Section: Discussionmentioning

confidence: 99%

“…35,40 As an example related to ROP, BDNF is important in ganglion cell maturation in the retina and is reduced during dark rearing of mice. 36 Recently, it was found that mice in utero reared in the dark or lacking the gene encoding melanopsin, which is involved in certain ganglion cell responses to light, 37 developed vascular anomalies that could predispose to conditions like ROP. 38 Additional clinical evidence that higher average day length during early gestation was associated with lower risk of ROP 42 provides an additional link among light, ganglion cell maturation, retinal vascular development, and reduced risk of later ROP.…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants Associated With Severe Retinopathy of Prematurity in Extremely Low Birth Weight Infants

Hartnett

Morrison

Smith

et al. 2014

Invest. Ophthalmol. Vis. Sci.

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Citation: Hartnett ME, Morrison MA, Smith S, et al. Genetic variants associated with severe retinopathy of prematurity in extremely low birth weight infants. Invest Ophthalmol Vis Sci. 2014;55:6194-6203. DOI: 10.1167/iovs.14-14841 PURPOSE. To determine genetic variants associated with severe retinopathy of prematurity (ROP) in a candidate gene cohort study of US preterm infants.METHODS. Preterm infants in the discovery cohort were enrolled through the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, and those in the replication cohort were from the University of Iowa. All infants were phenotyped for ROP severity. Because of differences in the durations of enrollment between cohorts, severe ROP was defined as threshold disease in the discovery cohort and as threshold disease or type 1 ROP in the replication cohort. Whole genome amplified DNA from stored blood spot samples from the Neonatal Research Network biorepository was genotyped using an Illumina GoldenGate platform for candidate gene single nucleotide polymorphisms (SNPs) involving angiogenic, developmental, inflammatory, and oxidative pathways. Three analyses were performed to determine significant epidemiologic variables and SNPs associated with levels of ROP severity. Analyses controlled for multiple comparisons, ancestral eigenvalues, family relatedness, and significant epidemiologic variables. Single nucleotide polymorphisms significantly associated with ROP severity from the discovery cohort were analyzed in the replication cohort and in meta-analysis.RESULTS. Eight hundred seventeen infants in the discovery cohort and 543 in the replication cohort were analyzed. Severe ROP occurred in 126 infants in the discovery and in 14 in the replication cohort. In both cohorts, ventilation days and seizure occurrence were associated with severe ROP. After controlling for significant factors and multiple comparisons, two intronic SNPs in the gene BDNF (rs7934165 and rs2049046, P < 3.1 3 10 À5 ) were associated with severe ROP in the discovery cohort and were not associated with severe ROP in the replication cohort. However, when the cohorts were analyzed together in an exploratory meta-analysis, rs7934165 increased in associated significance with severe ROP (P ¼ 2.9 3 10 À7 ).CONCLUSIONS. Variants in BDNF encoding brain-derived neurotrophic factor were associated with severe ROP in a large candidate gene study of infants with threshold ROP.

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“…Experimental studies provide links between the neurotrophic factor, brain-derived neurotrophic factor (BDNF), light-induced effects on ganglion cell maturation, and ROP. BDNF is important in ganglion cell maturation and is reduced in mice reared in the dark(58, 196). Several studies reported reduced circulating BDNF in extremely low birth weight infants, who developed ROP(77, 135), including in a study of extremely low birth weight infants enrolled through the US Neonatal Research Network.…”

Section: Advancements In Understanding the Pathophysiology Of Ropmentioning

confidence: 99%

Advances in understanding and management of retinopathy of prematurity

Hartnett

2017

Survey of Ophthalmology

109

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The understanding, diagnosis and treatment of retinopathy of prematurity (ROP) have changed in the last seventy years since the original description of retrolental fibroplasia associated with high oxygenation. It is now recognized that ROP differs in appearance world-wide and as ever smaller and younger premature infants survive. New methods are being evaluated to image the retina, diagnose severe ROP, and determine windows of time for treatment to save eyes and improve visual and neural outcomes. New treatments to promote physiologic retinal vascular development, vascular repair, and inhibit vasoproliferation by regulating proteins involved in vascular endothelial growth factor, insulin-like growth factor, or erythropoietin signaling. Reducing excessive oxidative/nitrosative stress and understanding progenitor cells and neurovascular and glial vascular interactions are being studied.

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Retinal TrkB receptors regulate neural development in the inner, but not outer, retina

Cited by 49 publications

References 83 publications

Rai1 frees mice from the repression of active wake behaviors by light

Rai1 frees mice from the repression of active wake behaviors by light

Genetic Variants Associated With Severe Retinopathy of Prematurity in Extremely Low Birth Weight Infants

Advances in understanding and management of retinopathy of prematurity

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