Abstract
Abstract: :
Purpose: Amblyopia is a common developmental disorder that can severely impair visual acuity. Although anatomical/physiological changes in visual pathways have been extensively studied, molecular mechanisms of amblyopia are largely unknown. Here, we used gene expression profiling techniques, along with laser capture microdissection (LMD), to determine expression patterns of neurons in non–deprived and deprived layers in the lateral geniculate nucleus (LGN) in a subhuman primate monocular deprivation model of amblyopia. Methods: Amblyopia was induced in macaque monkeys by monocular eyelid suture at birth. LGN were harvested at four months. LMD was used to obtain individual LGN layers for DNA microarray; pairwise comparisons were made between parvocellular and magnocellular layers in non–deprived layers and between non–deprived and deprived layers of the LGN. In situ hybridization was used in further analyses of specific genes. Results: Of 22,283 microarray probe sets, 281 transcripts (including 167 known genes) were enriched in the parvocellular layer (e.g., PACAP), while 212 transcripts (including 105 known genes) were magnocellular layer–enriched (e.g., CRH). Comparison of non–deprived with deprived layers showed differential expression of 66 transcripts distributed across both parvocellular and magnocellular layers; 48 transcripts were induced (e.g., DPR3) and 18 were repressed (e.g., NMOR2) in deprived layers. Selected genes were verified by Q–PCR and/or in situ hybridization. Conclusions: Identification of parvocellular layer– and magnocellular layer–enriched transcripts in non–deprived laminae identified transcripts potentially linked to the distinct visual processing roles of the two laminae. Only a relatively small number of genes exhibited altered expression in deprived LGN laminae of amblyopic monkeys. The patterned changes in genes expression, although modest, may play an important role in molecular pathogenesis of amblyopia.
Keywords: amblyopia • gene microarray