“Many of us take our eyes for granted; only when threatened with vision loss and partial or total blindness do we begin to realize what marvelous and valuable sense organs we possess.
Although the human eye contains several types of tissue, perhaps the most crucial for producing clear images is the retina. The retina is essentially a piece of brain tissue that projects through the back of the eye to receive input from the outside world – in the form of photons. Processing of the photons detected by retinal photoreceptors gives rise to our perception of images, movement, life and love.
Our laboratory studies the elaborate cellular architecture of retinal photoreceptors -- the rods and cones -- to understand their fundamental biology, and the cellular and molecular underpinnings for several forms of clinically significant inherited and acquired eye diseases.”
“Human vision begins with rod and cone photoreceptors, light-sensitive ciliated sensory neurons situated in the neural retina. These fragile cells are susceptible to a variety of insults, which can impede their function and viability and cause retinal degeneration and vision loss. Vertebrate animal models, and in particular mice, have been a valuable resource to identify molecules essential for normal photoreceptor physiology. Although a wide variety of naturally occurring and engineered mouse models have been investigated for retinal degeneration, and a majority of vision loss in inherited photoreceptor degenerations is known to result from secondary pathogenic processes, the detailed mechanisms by which genetic defects cause retinal degeneration continue to be debated. Further advances are needed to improve understanding of normal photoreceptor physiology and implement more effective clinical treatments. It is anticipated that insights into the relatively simple monogenic diseases can simultaneously shed light on widely prevalent loss-of-sight conditions with multifactorial etiologies.
The retinal degeneration slow (rds) mouse (also known as Prph2Rd2) has been the focus of numerous investigations of photoreceptor and retinal structure, function and viability. This naturally occurring model results from a spontaneous insertion of viral DNA into the rds (also known as Prph2) gene to produce a null allele. Complete loss of the gene product (peripherin/rds) in homozygous null animals prevents elaboration of rod and cone photoreceptor outer segments (OSs) – the specialized ciliary organelles upon which vertebrate light detection depends. Surprisingly, this massive structural defect is not catastrophic for photoreceptor viability. Instead, cells undergo a relatively slow rate of degeneration that occurs over a period of months, and has prompted evaluation of several therapeutic strategies.
A previous study applied a whole-retina microarray approach to the rds model to identify genes associated with retinal degeneration. Here, we investigate the global transcriptome response of purified rds rod photoreceptors to lack of peripherin/rds and absence of OSs. Our findings suggest that a combination of homeostatic mechanisms may contribute to the protracted time course of retinal degeneration in the rds retina.”