I.
Introduction
A. Clinical optometry as currently practiced is undergoing a fundamental, revolutionary transformation.
This transformation will change the way optometrists understand, classify, diagnose, treat and manage
disease.
B. The Human Genome Project and other revolutionary advances have started to increase and broaden the
importance of genetics/genomics in all health care. This revolution will alter eye care forever, and it
involves a tremendous change from the “old genetics” to the “new genetics.” Genetics is no longer an
esoteric academic specialty that involves rare diseases.
II. The “old genetics”
A. The old genetics dealt with conditions caused by a mutation in a single gene or by an extra or missing
chromosome or part of a chromosome.
B. These conditions are relatively rare. Most patients are not directly affected by them. Thus, these
conditions play a relatively small role in health care.
C. The conditions are rare enough that genetics care could be provided by medical geneticists and genetic
counselors, with occasional involvement of primary care providers
III. The “new genetics”
A. The new genetics emerged due to knowledge derived from the HGP.
B. All medical conditions have a genetic component and can be viewed through a “genetic lens.”
C. The new genetics deals with multifactorial conditions that are partly caused by mutation(s) in gene(s).
1. Multifactorial systemic conditions include diabetes, atherosclerosis, colon cancer, breast cancer, etc.
2. Multifactorial ocular conditions include the glaucomas, AMD, diabetic retinopathy, etc.
D. These conditions are common enough that genetics care will be supplied primarily by primary care
providers from many health disciplines with occasional involvement of medical geneticists and genetic
counselors.
E. The new genetics will provide a better understanding of the non-genetic (environmental) factors in
health & disease.
F. There will be a shift from an emphasis on disease treatment to health maintenance.
IV. Human Genome Project (HGP)
A. 15-year worldwide research effort (1990-2005).
B. HGP Goals
V. Proteomics – the newest revolution in a post-genomic era
A. What is proteomics?
B. Clinical applications
1. Early detection of disease using proteomic patterns of body fluid samples
2. Diagnostic tests - diagnosis based on proteomic signatures as a complement to histopathology
3. Individualized treatment - selection of therapeutic combinations that best target the entire
disease-specific protein network
4. Real-time assessment of therapeutic efficacy and toxicity
5. Rational modulation of therapy based on changes in the diseased protein network associated
with drug resistance
VI. Improved classification of diseases (e.g., RP, corneal dystrophies) will result from knowledge of the
gene involved and its correlation with the clinical expression of the disease.
VII. Improved understanding of pathophysiology – for example the genetics of the glaucomas:
A. Identification of genes for specific types of glaucoma
1. Optineurin (OPTN) – accounts for about 17% of POAG
2. Myocilin (MYOC/TIGR – GLC1A) – accounts for juvenile-onset OAG and about 4% of POAG
3. Cytochrome P4501B1 enzyme (CYP1B1 – GLC3A) – mutated in primary congenital glaucoma
4. Other glaucoma genes (9 other genes have been identified, but not cloned)
B. Future directions
1. Understanding glaucoma pathogenesis
2. Finding therapeutic interventions for treating glaucoma
3. Assisting in early detection of POAG
VIII. Improved diagnostic testing
A. Microarrays (DNA chips, RNA chips, Protein chips)
B.
C.
D.
E.
F.
1. Up to at least 400,000 probes can be put on the chips, and scans for matches can take as little as 5
minutes per chip.
2. Applications.
Microfluidics (lab-on-a-chip)
Point-of-care testing
Tests will become available in the next 10 years to determine risk for common diseases,
especially for those diseases for which there will be some form of treatment. Thinking will shift to
probabilities (statistical risks) instead of definitive answers.
OcuGene test (InSite Vision) – should optometrists be using this test?
Reasons for genetic testing
IX. Improved management/treatment options
A. Improved patient management will result from identification of patients with susceptibility genes
(e.g., GLC1 [MYOC] for juvenile-onset, open angle glaucoma).
B. Gene therapy and ocular diseases. The current active targets for gene therapy include neovascular
AMD (already in clinical trials), Leber congenital amaurosis, retinitis pigmentosa, and other inherited
retinal dystrophies.
C. Antisense technology and CMV retinitis.
D. RNA interference (RNAi). This is a new approach that is sparking a revolution in therapeutics &
functional genomics.
X. Genetic counseling – new role for primary care clinicians (including optometrists)
A. Genetic counseling will become more and more of a primary care responsibility.
B. There are not enough genetics counselors or medical geneticists to handle the increase in demand.
C. Every health care provider will become a genetic counselor in the next ten years.
XI. Pharmacogenomics
A. More than 100,000 people die each year from adverse responses to medications, and over 2 million
people have serious reactions. Some drugs work well in some patients and not as well in others.
B. Drug metabolism is under genetic control.
C. Anticipated benefits
1. Facilitation of drug discovery by creating drugs based on the RNA molecules, proteins, and
enzymes associated with genes and diseases.
2. Better, safer drugs at first use will be possible by knowing the patient’s genetic profile.
3. Better methods of determining appropriate drug dosages will also result.
4. Better vaccines can be made from DNA or RNA that will minimize risks.
5. Decreased total cost of health care will result form minimization of adverse drug reactions,
failed drug trials, and time-to-market for new drugs.
XII. Ethical, Legal, and Social Implications (ELSI).
XIII. Sources of continuing education on genomics, genetics, and clinical practice