Cataracts - Nutrition Research
The objective of the laboratory for Nutrition and Vision Research is to gather information regarding the etiologies of age-related eye lens cataract and age related maculopathy and to use that information to diminish risk for the progress or incidence of these debilities. These objectives are of critical importance not only because sight is one of our most precious senses, but also because these debilities result in the vast majority of blindness. In addition, costs associated with cataract treatment comprise the largest line item in the Medicare budget, some $5 billion. It is estimated that if we can delay cataract by only 10 years we can eliminate the need for half of the cataract extractions. It is important to realize that while there is a surgical remedy for most cataracts there are no cures for AMD; thus, a means to delay the debility is urgently needed.
To these ends we are conducting the following projects:
- Nutrition and Vision project
603 persons have been recruited from the Nurses' Health Study, had their ocular examination and had full dietary records obtained. Data gathered to date indicate that persons who consumed vitamin C supplements for over 10 years have 60-80% decreased risk ratio for cataract.
- Studies regarding the etiology of cataract: Relationship between dietary antioxidant levels and eye tissue antioxidant levels of ascorbate
Many epidemiological and biochemical studies indicate that eye aging is associated with oxidative stress and that such stress is cataractogenic. We are trying to determine diet-eye tissue relationships between antioxidants so as to be able to predict the minimum intake of various antioxidants which may provide the maximum antioxidant level in eye tissues. prior work from this group established that persons who consume ascorbate supplements have elevated eye tissue levels of this vitamin. Data were gathered for several hundred humans who were scheduled for cataract extractions. These data indicate that intake of 250 mg/day of ascorbate is sufficient to saturate eye tissues. Studies are progressing so that similar information can be obtained for other antioxidants.
- Studies regarding the etiology of cataract: Relationship between antioxidant intake and tissue levels in ODS rats
The ODS rat is a more durable animal than the guinea pig and is being developed for use in studies regarding the efficacy of antioxidants in delaying cataract. It is clear that the animals are unable to synthesize ascorbate, and diet/tissue relationships regarding ascorbate have been established. Many other parameters, i.e relationships between ascorbate and tocopherol and, possibly, GSH will also be pursued using the tissues from these animals. We will induce cataract with galactose and determine the efficacy of ascorbate in delaying that cataract.
- Use of Emory mice in studies regarding the etiology of cataract and determination of the means by which cataract is delayed by feeding animals calorie-restricted diets
A recent publication documented our success in delaying cataract, cancer and many other age-related phenomena in Emory mice which were fed diets restricted in calories. We are now in the process of evaluating a plethora of biochemical data related to the etiology of these diseases. We have expanded our investigations between protein turnover and dietary manipulations, since many diet-related differences in protein turnover were observed and since we hypothesize that altered protein turnover is associated with these diseases. The proteins of interest are the proteins which are involved in cataractogenesis and transcription factors which are involved in cell cycling and cancer.
- Studies regarding the etiology of cataract relationship between oxidation and protein turnover
Oxidation models in lens cells in culture have been perfected and cell viability established. Oxidation-related changes in cellular antioxidants have been determined, and the relationship between antioxidant levels, particularly glutathione, and lens protein turnover and protein marking by the ubiquitin system have been established. Rate-controlling steps for these processes have been determined.
- Studies regarding the etiology of age-related maculopathy (ARM) -Relationships between oxidation and protein turnover
A recently developed emphasis area in this laboratory is establishing the etiology of age-related maculopathy and then using nutrition to affect incidence of ARM. Oxidation models in retinas and retinal cells in culture have been perfected and cell viability established. Oxidation-related changes in cellular antioxidants have been determined, and the relationship between antioxidant levels, particularly glutathione, and retina protein turnover and protein marking by the ubiquitin system have been established. Rate-controlling steps for these processes have been determined. Since comparable phenomena seem to obtain for neural (pC12) cells, we are extending these investigations in the pC12 system.
A graphical summary of our work is provided in the following figure: