A retinal neuronal development wave of retinoschisin expression begins in ganglion cells during layer formation

Yuichiro Takada, Robert N. Fariss, Atsuhiro Tanikawa, Yong Zeng, Deborah Carper, Ronald Bush, Paul A. Sieving

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)


PURPOSE. Mutations in the retinoschisin gene, RS-1, cause juvenile X-linked retinoschisis (XLRS), a dystrophy characterized by delamination of the inner retinal layers, leading to visual impairment. Although the retinoschisin protein (RS) is expressed most abundantly in photoreceptors in the outer retina, XLRS disease affects the innermost retinal layers, including the nerve fiber layer that contains retinal ganglion cells (RGCs). Considering the histopathological and electrophysiological characteristics of the clinical disease, the present study was conducted to evaluate the local cellular expression of RS-1 during retinal development. METHODS. RS protein and RS-1 mRNA were localized to specific retinal cell types in embryonic to adult mice by immunohistochemistry, confocal immunofluorescence microscopy, catalyzed reporter deposition in situ hybridization, and laser capture microdissection/RT-PCR. RESULTS. RS-1 mRNA was expressed first in RGCs by postnatal day (P)1, after terminal differentiation. Expression then moved posteriorly through the retina in a spatial and temporal developmental wave, as additional neuronal classes were born and synaptic layers were formed. RS was expressed by bipolar cells at a time when these neurons were establishing functional synapses with photoreceptors, evidenced by the appearance of the electroretinogram b-wave between P12 and P14. CONCLUSIONS. All major classes of adult retinal neurons, with the possible exception of horizontal cells, express RS protein and mRNA, strongly suggesting that retinoschisin in the inner retina is synthesized locally rather than being transported, as earlier proposed, from distal retinal photoreceptors. Continued expression of RS by mature inner-retinal neurons supports the possibility of a therapeutic strategy of protein replacement to treat both infants and adults with XLRS.

Original languageEnglish
Pages (from-to)3302-3312
Number of pages11
JournalInvestigative Ophthalmology and Visual Science
Issue number9
Publication statusPublished - 09-2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'A retinal neuronal development wave of retinoschisin expression begins in ganglion cells during layer formation'. Together they form a unique fingerprint.

Cite this