Abstract
Abstract: :
Purpose: Fibroblast growth factor receptors (FGFR) are implicated in development and survivability of retinal cells. Currently there are four characterized FGFR and a newly described FGFR5. While the distribution of FGFR–1 through FGFR–4 have been characterized in the adult human retina, little is known about the time–course and position of specific FGFR in retinal development. In this study we have characterized the distribution of FGFR–1 through FGFR–5 in the human fetal and adult retina. Methods: Normal (absent any obvious genetic or other ocular/retinal abnormalities) fetal eyes aged 47–108 days post–conception were obtained from the Birth Defects Research Laboratory (Seattle, WA). The adult human eyes were obtained from One Legacy (Redlands, CA). The eyes were then fixed in 4% paraformaldehyde in 0.1 M PBS buffer, pH 7.4. After fixation the eyes were saturated in 30% sucrose, placed in 50% OCT for 20 minutes, blocked in OCT and frozen at –150 °C. The eyes were sectioned 10–20µm on a cryostat. Sectioned tissue was blocked with 10% horse serum, labeled with rabbit or goat antibody to the appropriate FGFR overnight. The appropriate Alexa–488 conjugated secondary antibody was then used to label FGFR expressing tissue. Digital images were captured from florescent microscopy. Results: Expression of FGFR–1 through FGFR–4 in the adult retina was similar to previous reports (Kinkl et al., Mol. Vis., 8:149–60, 2002). FGFR–1 was diffusely present in nerve fiber layer (NFL), ganglion cell layer (GCL), inner nuclear layer (INL), outer nuclear layer (ONL) as well as inner segments of rods and cones. FGFR–2 was distinctly present in the NFL, GCL, INL, and ONL. FGFR–3 was more prominent in the NFL and GCL, but present in the INL and inner segments of rods. FGFR–4 was diffusely present, but most prominent in the GCL and inner segments of rods and cones. FGFR–5 did not show significant labeling in the adult. The fetal retina expressed FGFR–1 through FGFR–5 throughout the represented developmental range. FGFR–1 through FGFR–4 labeling was present in the proliferating zone of the retina and was similar to the adult as distinct retinal layers developed. FGFR–5 was found only in the fetal NFL, GCL and in the boundary between neural retina and pigment epithelium. Conclusions: This study is the first to characterize the pattern of FGFR presence in the human fetal retina and the first to characterize the expression of FGFR–5. FGFR–1–4 mimics the expression of the adult retina and was present upon initial development of each retinal layer. FGFR–5 was present only at fetal ages in the inner retinal layers. Its expression correlates with the development of GCL and may be unique in their ontogeny.
Keywords: growth factors/growth factor receptors • retinal development • anatomy