Retinal degenerations are one of the most important causes of retinal dysfunction including blindness. The prevention and ultimately the cure of such diseases depends on understanding the cellular and molecular mechanisms responsible for the differentiation and maintenance of retinal cells. Formation of the retina requires orchestration of numerous complex cellular and molecular events. Cell division, migration, and differentiation result in a retina with well defined layers, each containing a limited number of cellular phenotypes. Generation of the appropriate number and type of cells is a complex problem and the cellular and molecular mechanisms which regulate these events are unknown. We propose experiments to address specific questions about retinal development using an organotypic retinal slice preparation combined with cellular and molecular probes. Using the retinal slice preparation, we will examine how cell fate is regulated in the retina. Does the fate of a retinal cell depend on its location at the time of division or is there a prior commitment to particular phenotype. To do this, we will transplant neuroepithelial progenitor cells to different locations within the retina using our newly developed retinal slice preparation to discover whether and how different microenvironments change the phenotypic fate of individual cells. We will also use the retinal slice preparation to test the effects of extracellular growth factors on retinal cell proliferation and differentiation. To understand what control the differentiation of newly generated rod photoreceptors, and what fraction of the newly divided outernuclear layer cells actually differentiate into rods, we will use in vivo experiments in the experimentally useful fish retina which continues to grow throughout life. We will label newly divided cells in the outer nuclear layer of the retina with a probe for opsin mRNA using in situ hybridization to determine what fraction of the new cells continue to differentiate into rod photoreceptors. We will also examine the effect of candidate factors on differentiation. Results from these experiments should help us understand normal retinal development but also the mechanisms leading to retinal dysfunction.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Hunter, Chyren
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Schools of Arts and Sciences
United States
Zip Code
Grens, Kerry E; Greenwood, Anna K; Fernald, Russell D (2005) Two visual processing pathways are targeted by gonadotropin-releasing hormone in the retina. Brain Behav Evol 66:1-9
Zhao, Sheng; Fernald, Russell D (2005) Comprehensive algorithm for quantitative real-time polymerase chain reaction. J Comput Biol 12:1047-64
Kroger, R H; Campbell, M C; Fernald, R D et al. (1999) Multifocal lenses compensate for chromatic defocus in vertebrate eyes. J Comp Physiol A 184:361-9
Kroger, R H; Campbell, M C; Munger, R et al. (1994) Refractive index distribution and spherical aberration in the crystalline lens of the African cichlid fish Haplochromis burtoni. Vision Res 34:1815-22
Kroger, R H; Fernald, R D (1994) Regulation of eye growth in the African cichlid fish Haplochromis burtoni. Vision Res 34:1807-14
Evans, B I; Fernald, R D (1993) Retinal transformation at metamorphosis in the winter flounder (Pseudopleuronectes americanus). Vis Neurosci 10:1055-64
Evans, B I; Harosi, F I; Fernald, R D (1993) Photoreceptor spectral absorbance in larval and adult winter flounder (Pseudopleuronectes americanus). Vis Neurosci 10:1065-71
Hagedorn, M; Fernald, R D (1992) Retinal growth and cell addition during embryogenesis in the teleost, Haplochromis burtoni. J Comp Neurol 321:193-208
Mack, A F; Fernald, R D (1992) Control of vertebrate retinal cell production. Exp Neurol 115:65-8
Mack, A F; Fernald, R D (1991) Thin slices of teleost retina continue to grow in culture. J Neurosci Methods 36:195-202

Showing the most recent 10 out of 16 publications