Decreased retinal ganglion cell number and misdirected axon growth associated with fissure defects in Bst/+ mutant mice

Dennis S. Rice, Qing Tang, Robert Williams, Belinda S. Harris, Muriel T. Davisson, Dan Goldowitz

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose. The autosomal semidominant mutation Bst (belly spot and tail) is often associated with small and atrophic optic nerves in adult mice and shares several important attributes with heritable optic nerve atrophy in humans. In this article, the authors present adult and developmental studies on the retinal phenotype in Bst/+ mice. Methods. Retinal ganglion cells in adult Bst/+ mice were labeled retrogradely with horseradish peroxidase injected into the right optic tract. Labeled ganglion cells were mapped in whole-mounted retinas ipsilateral and contralateral to the injection site. The number of axons in optic nerves of these and other cases were quantified using an electron microscopic method. Eyes of neonatal, embryonic day 15 (E15), and embryonic day 12 (E12) Bst/+ mutants were examined histologically to understand the etiology of the retinal phenotype. Results. Approximately 60% of adult Bst/+ mice have deficient direct pupillary light responses. This neurologic phenotype is associated with a reduction in the number of retinal ganglion cells from the wild-type average of 67,000 to less than 20,000 in Bst/+ mutants. Ganglion cells with crossed projections are more severely affected than those with uncrossed projections. Histologic analysis of eyes from E12 mice reveals a delayed closure of the optic fissure. Despite this abnormality, other ocular structures appear relatively normal. However, some E15 mutants exhibit marked disorganization of the retinal neuroepithelium, and ganglion cell axons are found between pigmented and neural retina. At birth, optic nerves of affected mice are smaller than those of wild-type mice, ectopic axons are found within the eyes, and the ganglion cell layer contains many dying cells. Conclusions. The expression of the retinal phenotype in Bst/+ mutants is highly variable-ranging from a complete absence of ganglion cells to numbers comparable to that in wild-type mice. The reduction in ganglion cell number in affected adult Bst/+ mice is attributable to the failure of ganglion cell axons to reach the optic nerve head early in development. Delayed fusion of the fissure is consistently associated with the Bst/+ genotype and probably contributes to the failure of ganglion cell axons to grow out of the eye.

Original languageEnglish (US)
Pages (from-to)2112-2124
Number of pages13
JournalInvestigative Ophthalmology and Visual Science
Volume38
Issue number10
StatePublished - Sep 1997

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Retinal Ganglion Cells
Axons
Tail
Cell Count
Ganglia
Growth
Optic Nerve
Phenotype
Retina
Optic Atrophy
Optic Disk
Horseradish Peroxidase
Nervous System
Genotype
Parturition
Electrons
Light
Mutation
Injections

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Decreased retinal ganglion cell number and misdirected axon growth associated with fissure defects in Bst/+ mutant mice. / Rice, Dennis S.; Tang, Qing; Williams, Robert; Harris, Belinda S.; Davisson, Muriel T.; Goldowitz, Dan.

In: Investigative Ophthalmology and Visual Science, Vol. 38, No. 10, 09.1997, p. 2112-2124.

Research output: Contribution to journalArticle

Rice, Dennis S. ; Tang, Qing ; Williams, Robert ; Harris, Belinda S. ; Davisson, Muriel T. ; Goldowitz, Dan. / Decreased retinal ganglion cell number and misdirected axon growth associated with fissure defects in Bst/+ mutant mice. In: Investigative Ophthalmology and Visual Science. 1997 ; Vol. 38, No. 10. pp. 2112-2124.
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abstract = "Purpose. The autosomal semidominant mutation Bst (belly spot and tail) is often associated with small and atrophic optic nerves in adult mice and shares several important attributes with heritable optic nerve atrophy in humans. In this article, the authors present adult and developmental studies on the retinal phenotype in Bst/+ mice. Methods. Retinal ganglion cells in adult Bst/+ mice were labeled retrogradely with horseradish peroxidase injected into the right optic tract. Labeled ganglion cells were mapped in whole-mounted retinas ipsilateral and contralateral to the injection site. The number of axons in optic nerves of these and other cases were quantified using an electron microscopic method. Eyes of neonatal, embryonic day 15 (E15), and embryonic day 12 (E12) Bst/+ mutants were examined histologically to understand the etiology of the retinal phenotype. Results. Approximately 60{\%} of adult Bst/+ mice have deficient direct pupillary light responses. This neurologic phenotype is associated with a reduction in the number of retinal ganglion cells from the wild-type average of 67,000 to less than 20,000 in Bst/+ mutants. Ganglion cells with crossed projections are more severely affected than those with uncrossed projections. Histologic analysis of eyes from E12 mice reveals a delayed closure of the optic fissure. Despite this abnormality, other ocular structures appear relatively normal. However, some E15 mutants exhibit marked disorganization of the retinal neuroepithelium, and ganglion cell axons are found between pigmented and neural retina. At birth, optic nerves of affected mice are smaller than those of wild-type mice, ectopic axons are found within the eyes, and the ganglion cell layer contains many dying cells. Conclusions. The expression of the retinal phenotype in Bst/+ mutants is highly variable-ranging from a complete absence of ganglion cells to numbers comparable to that in wild-type mice. The reduction in ganglion cell number in affected adult Bst/+ mice is attributable to the failure of ganglion cell axons to reach the optic nerve head early in development. Delayed fusion of the fissure is consistently associated with the Bst/+ genotype and probably contributes to the failure of ganglion cell axons to grow out of the eye.",
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T1 - Decreased retinal ganglion cell number and misdirected axon growth associated with fissure defects in Bst/+ mutant mice

AU - Rice, Dennis S.

AU - Tang, Qing

AU - Williams, Robert

AU - Harris, Belinda S.

AU - Davisson, Muriel T.

AU - Goldowitz, Dan

PY - 1997/9

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N2 - Purpose. The autosomal semidominant mutation Bst (belly spot and tail) is often associated with small and atrophic optic nerves in adult mice and shares several important attributes with heritable optic nerve atrophy in humans. In this article, the authors present adult and developmental studies on the retinal phenotype in Bst/+ mice. Methods. Retinal ganglion cells in adult Bst/+ mice were labeled retrogradely with horseradish peroxidase injected into the right optic tract. Labeled ganglion cells were mapped in whole-mounted retinas ipsilateral and contralateral to the injection site. The number of axons in optic nerves of these and other cases were quantified using an electron microscopic method. Eyes of neonatal, embryonic day 15 (E15), and embryonic day 12 (E12) Bst/+ mutants were examined histologically to understand the etiology of the retinal phenotype. Results. Approximately 60% of adult Bst/+ mice have deficient direct pupillary light responses. This neurologic phenotype is associated with a reduction in the number of retinal ganglion cells from the wild-type average of 67,000 to less than 20,000 in Bst/+ mutants. Ganglion cells with crossed projections are more severely affected than those with uncrossed projections. Histologic analysis of eyes from E12 mice reveals a delayed closure of the optic fissure. Despite this abnormality, other ocular structures appear relatively normal. However, some E15 mutants exhibit marked disorganization of the retinal neuroepithelium, and ganglion cell axons are found between pigmented and neural retina. At birth, optic nerves of affected mice are smaller than those of wild-type mice, ectopic axons are found within the eyes, and the ganglion cell layer contains many dying cells. Conclusions. The expression of the retinal phenotype in Bst/+ mutants is highly variable-ranging from a complete absence of ganglion cells to numbers comparable to that in wild-type mice. The reduction in ganglion cell number in affected adult Bst/+ mice is attributable to the failure of ganglion cell axons to reach the optic nerve head early in development. Delayed fusion of the fissure is consistently associated with the Bst/+ genotype and probably contributes to the failure of ganglion cell axons to grow out of the eye.

AB - Purpose. The autosomal semidominant mutation Bst (belly spot and tail) is often associated with small and atrophic optic nerves in adult mice and shares several important attributes with heritable optic nerve atrophy in humans. In this article, the authors present adult and developmental studies on the retinal phenotype in Bst/+ mice. Methods. Retinal ganglion cells in adult Bst/+ mice were labeled retrogradely with horseradish peroxidase injected into the right optic tract. Labeled ganglion cells were mapped in whole-mounted retinas ipsilateral and contralateral to the injection site. The number of axons in optic nerves of these and other cases were quantified using an electron microscopic method. Eyes of neonatal, embryonic day 15 (E15), and embryonic day 12 (E12) Bst/+ mutants were examined histologically to understand the etiology of the retinal phenotype. Results. Approximately 60% of adult Bst/+ mice have deficient direct pupillary light responses. This neurologic phenotype is associated with a reduction in the number of retinal ganglion cells from the wild-type average of 67,000 to less than 20,000 in Bst/+ mutants. Ganglion cells with crossed projections are more severely affected than those with uncrossed projections. Histologic analysis of eyes from E12 mice reveals a delayed closure of the optic fissure. Despite this abnormality, other ocular structures appear relatively normal. However, some E15 mutants exhibit marked disorganization of the retinal neuroepithelium, and ganglion cell axons are found between pigmented and neural retina. At birth, optic nerves of affected mice are smaller than those of wild-type mice, ectopic axons are found within the eyes, and the ganglion cell layer contains many dying cells. Conclusions. The expression of the retinal phenotype in Bst/+ mutants is highly variable-ranging from a complete absence of ganglion cells to numbers comparable to that in wild-type mice. The reduction in ganglion cell number in affected adult Bst/+ mice is attributable to the failure of ganglion cell axons to reach the optic nerve head early in development. Delayed fusion of the fissure is consistently associated with the Bst/+ genotype and probably contributes to the failure of ganglion cell axons to grow out of the eye.

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