Overview

Dr. Sandell’s laboratory is interested in the structure and function of the visual system, especially the changes that occur when the system is perturbed by genetic defects, normal aging, and injury. Our current work is divided into three areas:

1. Studies of retinal remodeling in retinitis pigmentosa
2. Studies of the effects of normal aging on the structure of the brain

Retinal Remodeling

Retinal ganglion cell axonsin the nerve fiber layer are abundant and have a normal trajectory in this donor retina from a patient with RP (SMI 31 immunohistochemistry)

Retinitis pigmentosa (RP) is the leading genetic cause of blindness. We are part of a large team, the Boston Retinal Implant Project, which is trying to develop a prosthesis which could be implanted into the eye to provide visual signals to patients with RP. RP is a progressive disease that results in the destruction of the photoreceptors, usually by young adulthood. However, there is substantial survival of the remaining retinal neurons, and the pathway to the brain remains intact. It is the goal of our team, and others, to build a device that could electrically stimulate the remaining neurons in the retina. These signals would then be transmitted to the brain and might provide a measure of useful vision analogous to the way electrical signals from cochlear implants provide useful signals for some deaf people. The role of our lab in this effort is to describe the anatomy of the retina in RP, to help guide the design and deployment of the prosthesis. We have also worked to develop and test a rabbit model of inducible photoreceptor degeneration, and were recently funded to determine whether neurotrophin-eluting hydrogels can retard or prevent retinal degeneration in a rodent model of RP.

The left panel shows a section through the visual streak of the normal rabit retina. This is the location of the highest neuron density in all layers. The right panel shows the visual streak four weeks after systemic treatment with indole acetic acid. The photoreceptors are eliminated.

Normal Aging

Aging causes impairments in memory and cognition, even in the absence of Alzheimer Disease. We participate in a Program Project Grant that uses Rhesus monkeys as a model for normal human aging. In the past we have worked with Dr. Alan Peters to examine the structure of the optic nerve and the anterior commissure in these animals, as examples of circumscribed white matter tracts. We have found extensive changes in myelin and loss of nerve fibers in all locations. Our next goal is to use immunohistochemistry to examine ubiquitin in the aging brain, to determine which cellular elements are targeted for destruction by this system.

Publications

The publications from our laboratory include those on aging in the optic nerve and brain of the monkey, and retinal development and degeneration in the zebrafish. We also have several manuscripts in preparation or editorial revision that present recent results regarding cell survival after toxic destruction of photoreceptors, and the persistent expression of developmental markers such as nestin and CHX-10 in the human eye with retinitis pigmentosa. For a complete list of publications please see the individual pages for the members of the lab.

Sandell, J.H., Peters, A. 2003. Disrupted myelin and axon loss in the anterior commissure of the aged rhesus monkey. J. Comp. Neurol., 466: 14-30.

Sandell, J.H., Peters, A. 2002. Effects of age on the glial cells in the rhesus monkey optic nerve. J. Comp. Neurol., 445:13-28.

Sandell, J.H., Peters, A. 2001. Effects of age on nerve fibers in the rhesus monkey optic nerve. J. Comp. Neurol. 429:541-553.

Daly, FJ, Sandell, JH. 2000. Inherited retinal degeneration and apoptosis in mutant zebrafish. Anatomical Record, 258: 145-155

Sandell, J.H. 1998. GABA as a developmental signal in the inner retina and optic nerve. Perspectives Dev. Neurobiol., 5 : 269-278.

Methodology

Light Microscopy

We use light microscopy to examine sections of retina and brain after using techniques to label whole cell populations or specific subpopulations of neurons or glia.

Immunohistochemistry

We use antibodies directed at particular proteins to label the cells containing those proteins. The antibody is then visualized by light microscopy. These studies use wholemount pieces of retina, or frozen sections of retina or brain cut on a cryostat or sliding microtome. The proteins of current interest include opsin, calbindin D-28, protein kinase C, vimentin, nestin, CHX-10 and ubiquitin.

Semithin Plastic Sections

Pieces of retina are embedded in plastic and cut as two micron thick sections to allow detailed examination of retinal morphology with the light microscope. These sections are often drawn with the aid of a camera lucida to allow measurements to be made of layer thickness and other parameters.

Tissue Sources

We use human donor eyes for our work on retinitis pigmentosa. These are supplied by the Foundation Fighting Blindness. We also examine rabbit retinas in our efforts to develop an inducible model of photoreceptor degeneration, and shortly we will begin to use rodents with mutations that lead to retinal degeneration, to determine whether neurotrophin-eluting hydrogels are therapeutic in this model. Our work on aging uses tissue obtained from young and old rhesus monkeys.

People

Julie Sandell Ph.D.
Dr. Sandell is the director of the laboratory. She received her doctorate from the Massachusetts Institute of Technology. Dr. Sandell is broadly interested in the str ucture of the visual system, particularly the way in which it responds to the perturbations o f genetic defects and aging.

Patrick A Scott Ph.D.
Patrick A. Scott completed his B.S. at Canisius College, his Master of Science in Vision Science as well as a Doctor of Optometry degree at The New England College of Optometry.