Inner retinal abnormalities in a mouse model of Leber's congenital amaurosis

J Comp Neurol. 2004 Feb 9;469(3):351-9. doi: 10.1002/cne.11019.


Leber's congenital amaurosis (LCA) is the earliest and most severe form in the world of genetic retinal dystrophy causing blindness. An animal model of LCA was recently created in which the cone-rod homeobox (crx) gene was disrupted using homologous recombination. Crx-/- mice display abnormal development of photoreceptors followed by their degeneration. We analyzed the morphology of inner retinal cells in crx-/- mice in order to evaluate the effects of abnormal photoreceptor development and death upon other retinal neurons. The identification of a time window during which inner retinal cells are still viable could be very important in view of the possibilities that photoreceptor transplantation or gene therapy might be used to restore vision in LCA. We used a combination of immunocytochemical and confocal microscopy techniques to screen the crx-/- inner retina and verify its morphological integrity after photoreceptor degeneration. We found significant morphological alterations in second-order neurons in crx-/- animals. The appearance of mutant retinas after photoreceptor death is indistinguishable from that of the retinal degeneration (rd/rd) mouse, a different genetic model of a retinal disease characterized by photoreceptor degeneration. However, at early stages of photoreceptor degeneration the morphology of retinal cells in the crx-/- mutant is considerably well preserved. It is likely that different genetic mechanisms that cause abnormal photoreceptor development and/or degeneration lead to a common pathway that determines second-order neuron modifications. The severity of modifications is linked to the timing of onset of the degeneration and appears to increase with time.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn
  • Cell Count
  • Choline O-Acetyltransferase / metabolism
  • Disease Models, Animal
  • Embryo, Mammalian
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • Homeodomain Proteins / genetics
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism
  • Neurites / metabolism
  • Neurons / metabolism
  • Neurons / pathology
  • Optic Atrophy, Hereditary, Leber / pathology*
  • Parvalbumins / metabolism
  • Photoreceptor Cells / metabolism
  • Photoreceptor Cells / pathology
  • Protein Kinase C / metabolism
  • Protein Kinase C-alpha
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, Neurokinin-3 / metabolism
  • Retina / growth & development
  • Retina / pathology*
  • Trans-Activators / genetics
  • Tyrosine 3-Monooxygenase / metabolism


  • Homeodomain Proteins
  • Nerve Tissue Proteins
  • Parvalbumins
  • Receptors, Metabotropic Glutamate
  • Receptors, Neurokinin-3
  • Trans-Activators
  • cone rod homeobox protein
  • metabotropic glutamate receptor 6
  • Tyrosine 3-Monooxygenase
  • Choline O-Acetyltransferase
  • Prkca protein, mouse
  • Protein Kinase C
  • Protein Kinase C-alpha
  • GTP-Binding Protein alpha Subunits, Gi-Go