Macular Degeneration Research Center at the Yale Eye Center

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Macular degeneration and its multiple forms are the major cause of legal blindness in the over 65 population in this country. There are no adequate treatments to slow or cure this progressive disease. Thought to be a natural part of aging, recent studies have clearly shown that macular degeneration is a disease with multiple related causes. One theory is that it is a local form of hardening of the arteries, arteriosclerosis. It is also becoming clear that mutations in specific genes can cause or greatly increase the chances of developing macular degeneration. There are basically two clinical forms of age-related macular degeneration (AMD), the more common "dry" type and the less common but more visually debilitating "wet" type. Currently, only 10-15% of the estimated 500,000 patients who develop wet AMD worldwide every year are eligible for existing treatments.

But think of these facts: Macular degeneration is the leading cause of new cases of blindness in America each year, more than glaucoma and diabetic retinopathy combined. Currently, more than 13 million Americans suffer from the disease, and as the U.S. population ages, the number of macular degeneration patients will soon reach epidemic proportions. More than 30% of the population who are age 65 and older suffer from some from of macular degeneration.

At Yale Eye Center, they are searching for answers to prevent blindness from macular degeneration. The ultimate goal is to find the underlying genetic causes and contributing factors to prevent the development of macular degeneration. To that end, scientists work in their laboratories in the molecular biology (i.e., the study of genetic defects and how they can be corrected) and related areas.

Primary funding is required to support research into macular degeneration. The Yale Eye Center will utilize these funds for leadership recruitment and development, and for laboratory equipment. Recruitment of outstanding scientists and equipment purchases are the priorities. Such equipment includes an automated DNA sample preparer, a semi-automated DNA sequencer, and an electrophoresis system capable of detecting single base changes in DNA. The cost of these instruments is in the $15,000 to $75,000 range.

Project Funding

Project Income
	Connecticut Lions Eye Research Foundation
		Club Pledges Multiple District 23		225,000
		Committee of 100		100,000
		Special Events Multiple District 23		100,000
		LCIF Grant		75,000
				$500,000
	Yale Advisory Board			$4,500,000
Total Project Income				$5,000,000
Project Expenses
	Connecticut Lions Eye Research Foundation
		Upgraded bioinformatics capabilities		100,000
			Computer, networking, etc.
		Imaging Systems		100,000
			Microscopes, confocal, etc.
		Molecular biology equipment and resources		200,000
			DNA sequencer, real time PCR, etc.
		Biochemistry Equipment		100,000
			Chromatography, centrifuges, etc.
					$500,000
	Yale Advisory Board
		Endowed Research Professorship		2,500,000
			To recruit and support a world class scientist
		Endowed Research Fund		1,000,000
			For laboratory start-up and support
		Endowed Fellowships		500,000
			To support young scientists
		Current Use Funds		500,000
			To support immediate research needs and campaign costs
						$4,500,000
Total Project Expenses					$5,000,000

Equipment needs to build a Center for Macular Degeneration in the Department of Ophthalmology and Visual Sciences at Yale

Our first priority in building a Center for Macular Degeneration is to recruit new faculty. We currently have four faculty doing research on problems associated with Macular Degeneration, namely Drs. Colin Barnstable, Ray Gariano, Thomas Hughes and Ning Tian, together with two clinical faculty working on retinal problems, namely Drs. Kathleen Stoessel and Daniel Berinstein. They all have needs. However, the highest need will be for equipment to bring in one or two new faculty members. These may include a molecular biologist, a cell biologist, a biochemist, and/or an electrophysiologist. The following list is therefore arranged under those four headings. Because the exact models and capabilities of equipment are changing so rapidly, the following examples are only illustrative.

Molecular Biology equipment

An item needed would be a DNA sequencer, since our current sequencer is becoming inadequate for our needs. Upgrading this to a multichannel instrument will cost approximately $60,000. Quantitative assessment of gene expression in cells is a vital technique and has become much simpler with the introduction of real time PCR instruments The best instrument currently available has a list price of $55,000. Many operations in molecular studies are repetitive and can be automated. Introduction of robotic equipment will substantially enhance our productivity. An automated molecular biology workstation can carry out many of the routine operations involved in DNA cloning and analysis and can handle many times the number of samples that can be handled by a technician. It can also operate 24 hours a day and thus can more than double our output of certain procedures. The best model currently available is the Qiagen BioRobot 3000, which has a list price of approximately $50,000.

Several groups are now working with viruses to induce expression of genes in specific cell types. At present this work is being carried out in our tissue culture facility. This is far from ideal. We need to have a separate culture facility containing culture hood, incubator, microscope and miscellaneous equipment. The cost of a small, self-contained culture facility will be approximately ($35,000).

Molecular studies require sophisticated analysis of sequence and structural data comparing lab data with large databases maintained by the National Library of Medicine in Washington. Anatomical studies using digitized color images have replaced traditional paper photography. These images can be used to build up three-dimensional views of eye structures or can be assembled in time to provide movies of molecular events. To allow these studies we anticipate needing at least three high-speed computers with large monitors and appropriate peripheral devices. Currently each computer system would cost approximately $12,000 each for a total of $36,000. Networking these computers and purchasing appropriate software and software licenses will cost approximately $14,000.

In addition to computing power we need to upgrade our input devices and printers. We need high-resolution digital cameras on two of our microscopes ($25,000 total), a digitizing camera on a gel photography system ($10,000) and a photographic quality color printer ($15,000).

Cell Biology equipment

We currently have a calcium imaging system that works well to follow slow changes in cells. To study calcium changes at synapses we need to increase the speed of this system. This can be done for approximately $25,000. Our confocal microscope is beginning to show its age. We would like to trade it in for a better model and anticipate that this could be done with an additional $75,000 cost.

Biochemistry equipment

We have an increasing need to purify recombinant proteins. Equipment needed to accomplish this includes a new small ultracentrifuge (Approx. $35,000), a low pressure chromatography system ($12,000) and a medium pressure chromatography system ($30,000). To produce the recombinant proteins we need to increase our culture capacity by the purchase of a shaker incubator ($7,000) and a roller culture system ($13,000). We also have an urgent need to increase our freezer storage capacity by the purchase of a new -80° C freezer ($8,000).

Electrophysiology equipment

For those who are interested in the study of retinal function, particularly a small area of retina, in-patients with macular degeneration, or monitoring the progress of retinal function in animal model with retinal diseases such as retinal degeneration, a multifocal ERG recording system would be useful. ERG recording is a non-invasive task. It can be used repetitively on patients and animals. A typical multifocal ERG recording set can measure the retinal light response from over 100 locations in 50 degrees of the range with 2 degrees of spatial resolution simultaneously. A typical multifocal ERG set costs approximately $60,000.

Recruitment of a physiologist would require a patch-clamp system for recording from retinal neurons, including an upright microscope ($25,000-$45,000), an IR image system attached to the microscope ($5,000-$15,000), 1 or 2 sets of micromanipulators ($5,000-$20,000), an amplifier with data acquisition software and accessories ($10,000-$15,000), a computer ($2,000-$3,000), a system to deliver appropriate light stimulus ($1,000-$10,000), a retinal dissection setup ($5,000) and other accessories such as airtable and cages ($10,000-$20,000). Generally speaking, one such setup will cost $70,000 to $100,000.