TY - JOUR
T1 - Evidence of decreased adhesion between the neural retina and retinal pigmented epithelium of the Mitf(vit) (vitiligo) mutant mouse
AU - Bora, N.
AU - Defoe, D.
AU - Smith, S. B.
N1 - Funding Information:
This work was supported by NIH (EY09682 to S.B.S. and EY07036 to D.M.D.), by the Medical College of Georgia Research Institute, and by an unrestricted grant from Research to Prevent Blindness, New York, to the Department of Ophthalmology, Medical College of Georgia. The C57BL/6-Mitfvit mice were the offspring from our colony of breeding pairs that were provided by Dr. R. L. Sidman, New England Regional Primate Research Center, Southboro, Mass., USA (funded by NEI grant EY 06859).
PY - 1999
Y1 - 1999
N2 - In order for the retina to function properly, photoreceptor cell outer segments must be in contact with the adjacent retinal pigmented epithelium (RPE). A mouse model homozygous for the vitiligo mutation of the microphthalmia (Mitf) gene manifests disruption of the outer segment/RPE interdigitation and demonstrates progressive loss of the photoreceptor cells. The mouse nevertheless has near normal levels of rhodopsin for many weeks and it is not known whether there is an in vivo loss of adhesion or whether the disruption is visible following tissue processing for histology. To assess this, a mechanical separation experiment was performed in which neural retinas were peeled free from the RPE and examined for the amount of pigment adherent to them. The peeling experiment indicated that control neural retinas retained significant amounts of adherent pigment at all ages examined. Neural retinas of mutant mice at age 2 weeks demonstrated adherent pigment, but older animals retained minimal pigment. Scanning electron microscopy indicated that the RPE cells of control mice were markedly damaged upon peeling and displayed different planes of cleavage, whereas those of mutants showed minimal cellular damage upon peeling, suggestive of decreased adhesion. A recombination experiment revealed that the mutant RPE/eyecup could reappose mutant and control retinas under in vitro conditions, suggesting that RPE fluid transport abilities were intact. The data provide the first direct experimental evidence that the Mitf(vit) mutant mouse has a naturally occurring retinal detachment and hence support its value as a model for studies of retina/RPE adhesion.
AB - In order for the retina to function properly, photoreceptor cell outer segments must be in contact with the adjacent retinal pigmented epithelium (RPE). A mouse model homozygous for the vitiligo mutation of the microphthalmia (Mitf) gene manifests disruption of the outer segment/RPE interdigitation and demonstrates progressive loss of the photoreceptor cells. The mouse nevertheless has near normal levels of rhodopsin for many weeks and it is not known whether there is an in vivo loss of adhesion or whether the disruption is visible following tissue processing for histology. To assess this, a mechanical separation experiment was performed in which neural retinas were peeled free from the RPE and examined for the amount of pigment adherent to them. The peeling experiment indicated that control neural retinas retained significant amounts of adherent pigment at all ages examined. Neural retinas of mutant mice at age 2 weeks demonstrated adherent pigment, but older animals retained minimal pigment. Scanning electron microscopy indicated that the RPE cells of control mice were markedly damaged upon peeling and displayed different planes of cleavage, whereas those of mutants showed minimal cellular damage upon peeling, suggestive of decreased adhesion. A recombination experiment revealed that the mutant RPE/eyecup could reappose mutant and control retinas under in vitro conditions, suggesting that RPE fluid transport abilities were intact. The data provide the first direct experimental evidence that the Mitf(vit) mutant mouse has a naturally occurring retinal detachment and hence support its value as a model for studies of retina/RPE adhesion.
KW - Microphthalmia transcription factor
KW - Mouse
KW - Retinal degeneration
KW - Retinal pigment epithelium
KW - Vitiligo (C57BL/6-Mitf(vit))
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U2 - 10.1007/s004410051213
DO - 10.1007/s004410051213
M3 - Article
C2 - 9931354
AN - SCOPUS:0032895119
SN - 0302-766X
VL - 295
SP - 65
EP - 75
JO - Cell and Tissue Research
JF - Cell and Tissue Research
IS - 1
ER -