PMID- 11431429
OWN - NLM
STAT- MEDLINE
DCOM- 20010802
LR  - 20171213
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 42
IP  - 8
DP  - 2001 Jul
TI  - Delayed dark-adaptation and lipofuscin accumulation in abcr+/- mice: implications 
      for involvement of ABCR in age-related macular degeneration.
PG  - 1685-90
AB  - PURPOSE: To examine the ocular phenotype in mice heterozygous for a null mutation 
      in the abcr gene. METHODS: Retinas and retinal pigment epithelia (RPE) were 
      prepared from wild-type, abcr+/-, and abcr-/- mice. Fresh tissues were 
      homogenized and analyzed by normal phase high-performance liquid chromatography 
      (HPLC) for the presence of retinoids and phospholipids. In another study, fixed 
      tissues were sectioned and analyzed by light and electron microscopy. Finally, 
      anesthetized mice were studied by electroretinography (ERG) at different times 
      after exposure to strong light. RESULTS: A2E, the major fluorophore of 
      lipofuscin, and its precursors, A2PE-H(2) and A2PE, were approximately fourfold 
      more abundant in 8-month-old abcr+/- than in the wild-type retina and RPE. The 
      levels of these substances in abcr+/- mice were approximately 40% those in 
      abcr-/- mice. Lipofuscin pigment-granules were also visible in abcr+/- RPE cells 
      by electron microscopy. Accumulation of A2PE-H(2) and A2E in abcr+/- retina and 
      RPE, respectively, was strongly dependent on light exposure. Heterozygous mutants 
      also exhibited delayed recovery of rod sensitivity by ERG. This delay was 
      correlated with elevated levels of all-trans-retinaldehyde (all-trans-RAL) in 
      retina after a photobleach and was not caused by a reduction in quantum-catch due 
      to depletion of 11-cis-retinaldehyde (11-cis-RAL). CONCLUSIONS: Partial loss of 
      the ABCR or rim protein is sufficient to cause a phenotype in mice similar to 
      recessive Stargardt's disease (STGD) and age-related macular degeneration (AMD) 
      in humans. These data are consistent with the suggestion that the STGD 
      carrier-state may predispose to the development of AMD.
FAU - Mata, N L
AU  - Mata NL
AD  - Jules Stein Eye Institute, UCLA School of Medicine, 100 Stein Plaza, Los Angeles, 
      CA 90095-7008, USA.
FAU - Tzekov, R T
AU  - Tzekov RT
FAU - Liu, X
AU  - Liu X
FAU - Weng, J
AU  - Weng J
FAU - Birch, D G
AU  - Birch DG
FAU - Travis, G H
AU  - Travis GH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Abca4 protein, mouse)
RN  - 0 (Lipofuscin)
RN  - 0 (Retinoids)
RN  - 0 (retinylidene chromophore)
SB  - IM
MH  - ATP-Binding Cassette Transporters/genetics/*physiology
MH  - Animals
MH  - Chromatography, High Pressure Liquid
MH  - *Dark Adaptation
MH  - Electroretinography
MH  - Lipofuscin/*metabolism
MH  - Macular Degeneration/genetics/*metabolism/pathology
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Phenotype
MH  - Pigment Epithelium of Eye/metabolism
MH  - Retinoids/metabolism
MH  - Rod Cell Outer Segment/*metabolism/ultrastructure
EDAT- 2001/06/30 10:00
MHDA- 2001/08/03 10:01
CRDT- 2001/06/30 10:00
PHST- 2001/06/30 10:00 [pubmed]
PHST- 2001/08/03 10:01 [medline]
PHST- 2001/06/30 10:00 [entrez]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1685-90.