Last modified on October 13, 2008. . 

Rod Photoreceptors

The development of photoreceptors has been the subject of considerable investigation over the past 15 years.   While studying the development of photoreceptors in dissociated cell cultures, we found that their maturation is regulated by signals from neighboring cells.   Since these early studies, we, and others, have identified several factors that can promote the differentiation of rod photoreceptors in dissociated cell cultures.   The factors currently known to promote rod photoreceptor differentiation and/or opsin expression include:

Retinoic acid: Kelley et al, 1994 Development. 120(8):2091-102.Kelley et al, 1999 Neuroreport. 10(11):2389-94
Sonic hedgehog: Levine et al, 1997 J Neurosci. 17(16):6277-88.
Activin: Davis et al, 2000 Mol Cell Neurosci. 15(1):11-21.

Our current studies are directed to understanding how these and other factors regulate key transcriptional regulators involved in rod photoreceptor development, as well as investigations into the factors that control cone photoreceptor development.

Shown at the left are the effects of retinoic acid on E18 rat retinal cells. The left panels (E,C) show recoverin-immunoreactive cells in control cultures, while the right panels (B,D) show sister cultures treated with retinoic acid. E shows a combined labelling with recoverin and CRABP to show both photoreceptors and amacrine cells in these cultures.

Cone photoreceptors

We are also interested in cone photoreceptor development, and we have identified thyroid hormone and two nuclear hormone receptors, TRß2 and RXRgamma, as key regulators in this process.   This work has been carried out as a very productive collaboration with the lab of Douglas Forrest at the NIH.

The mammalian retina has two basic types of cones: the S-opsin (or blue) cones and the M-opsin (or green) cones. As cells become postmitotic and are committed to become some type of photoreceptor (P). The “default” fate appears to be the S-opsin expressing cone.   If the cell expresses Nrl, it will develop as a rod photoreceptor ( R).   If instead, the cell expresses TRß2 and RXRgamma, it will develop as either an S-opsin expressing cone (S) , or as an M-opsin expressing cone (M), depending on the local concentration of thyroid hormone (T3).

Roberts MR, Hendrickson A, McGuire CR, Reh TA. Invest Ophthalmol Vis Sci. 2005 46(8):2897-904.

Ng L, Hurley JB, Dierks B, Srinivas M, Salto C, Vennstrom B, Reh TA, Forrest D.

Nat Genet. 2001 Jan;27(1):94-8.

Roberts MR, Srinivas M, Forrest D, Morreale de Escobar G, Reh TA. Proc Natl Acad Sci U S A. 2006103(16):6218-23