Human fetal optic nerve: Overproduction and elimination of retinal axons during development

Abstract

We have estimated the number of axons in the optic nerves of human fetuses ranging in gestational age from approximately 10 to 33 weeks. At 10-12 weeks of gestation there were an estimated 1.9 million axons in the optic nerve. A peak count of 3.7 million axons was obtained from a specimen of 16-17 weeks gestation. The estimated number of axons then declined, stabilizing at an estimated 1.1 million axons by about week 29 of gestation. This figure is in close agreement with an estimate of 1.1-1.3 million optic axons in the human adult optic nerve. The results indicate that at least 70% of optic axons generated during development of the primary visual pathway are lost during fetal life. Part of this loss probably occurs as a result of the refinement of the terminal distribution of ganglion cell projections within their target nuclei. The significance of the relatively prolonged period of axonal loss is discussed.

Math5 (Atoh7) gene dosage limits retinal ganglion cell genesis

“…The potentially discordant effects of the ATOH7 genotype on adult RGC number between humans and mice may indicate species differences in genetic heterogeneity, which was absent in our comparison between inbred littermates, or the degree of developmental culling. The overall extent of culling is comparable in mice and humans, involving two-thirds of new RGCs [8,11], but the genetic background can influence birth and death independently [2]. Our results suggest that Math5 dosage affects RGC genesis, but other mechanisms compensate to ensure the proper number of functional ganglion cells in adults (Fig.…”

“…RGC axons coalesce to form the optic nerve and project to brain visual centers. More than 60% of new RGCs are lost by apoptosis during the period of synaptic refinement, which occurs during the first postnatal week in mice and during late gestation in primates [2,[8][9][10][11]. RGC survival is believed to reflect the formation of functional synaptic connections in the brain [10].…”

Optic nerve axons: life and death before birth

“…47 Apoptosis or (genetically) programmed cell death plays an important role in the development of RGCs and their axons. [48][49][50][51] Recently, interest has been focussed on the process of perverted apoptosis that may occur in diseases such as glaucoma (Table 1). 52 Developing RGC axons in the chiasm Normal vision is dependent on ordered neuronal maps of visual space which depend on precise connections between retinal axons and their target cells.…”

“…49,50 The lumen of the optic stalk is initially open and in communication with the forebrain cavity. It closes by the end of the second month of gestation, when it elongates and the foetal fissure is formed.…”

OCT Changes In Unilateral Amblyopia Patients, Using OPKOS SLO/OCT: A Cross Sectional Study

“…At 16-17 weeks of gestation, the estimated number of axons are 3.7 million. The number of axons in the human adult optic nerve is 1.1 million (Provis et al, 1965). [4] It was hypothesized that amblyopia may affect the postnatal maturation of the retina including the postnatal reduction of retinal ganglion cells,hence the macular and RNFL thickness might be increased in amblyopic eyes.…”