Medical Hypotheses 6: 427430, 1980

GLAUCOMA, "AUDITORY GLAUCOMA", "ARTICULAR GLAUCOMA" AND THE THIRD EYE

Donald 0. Rudin, Department of Molecular Biology, Eastern Pennsylvania Psychiatric Institute, Henry Avenue and Abbottsford Road, Philadelphia, Pennsylvania 19129.

ABSTRACT

Glaucoma may be one of a set of "baropathic" disorders in- cluding tinnitus, Meniere's disease, arthritis and bursitis caused by transport dysfunction in the "tissue membranes" of the set of closed "tissue cells" envisioned by The Tissue Cell Theory of Metazoa and which result, in turn, from prostaglandin distur- bances induced by primary or secondary essential fatty acid de- ficiencies possibly coupled with immunopathic effects.

Key Words: ageing spots, arthritis, basal lamina, bursitis, colchicine, cortisol, epinephrine, essential fatty acid defi- ciency, glaucoma, immune complex, linoleic acid, linolenic acid, lipid, melatonin, Meniere's, pigment, pineal, prostaglandin, serotonin, tinnitus, trabecular meshwork.

INTRODUCTION

Melatonin, the hormone of the pineal gland or "third eye", may regulate the diurnal physiology of the first two eyes and be useful in the treatment of glaucoma as well as tinnitus and Meniere's disease, here viewed as auditory "glaucoma", and in arthritis viewed as articular "glaucoma".

1. Melatonin is a serotonin derivative related to agents already used in the treatment of glaucoma.

2. Melatonin is thought to oppose the action of cortisol (1) to which many glaucoma patients are hypersensitive.

3. Melatonin may augment the conversion of essential fatty acids to prostaglandins (1) which reduce intraocular pressure following topical and possibly oral application (2).

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4. Melatonin reduces pigment dispersion in the eye (3) and skin (4) of mammals and, therefore, could reduce the load on the tra- becular meshwork in pigmentary glaucoma just as the exceptional effect of epinephrine derivatives (5) may result from action on pigment metabolism under adrenergic control (6).

5. By regulating lipid metabolism of cell membranes melatonin may control basal lamina turnover in the meshwork, thickening of which is the earliest known defect in glaucoma (7). Similar problems in the iris and lens may induce exfoliation imposing an extra load (8).

6. Lipid and basal lamina disturbances suggest a primary or se- condary immunopathy possibly of immune complex type involving either auto or environmental allo-antigens and so place glaucoma in the set of basal laminar diseases affecting all "transport organs", a newly defined organ group based on a general cell theory of biology including metazoa as well as the unizoa of the restricted Schwann cell theory (9, 10).

7. Melatonin is a hormone in search of a function. It may re- gulate diurnal physiology by inducing repose in opposition to steroidal stress effects, enhance night vision by contracting retinal and choroidal pigments and contribute to the normal diurnal fluctuation of intraocular pressure.

8. Following a nonspecific viral infection in a 56 year old white male I have observed a syndromic onset of open angle glau- coma, moderate tinnitus and the first ageing spots. Osmotic tests and fistulary relief are used in both glaucoma and laby- rinthine disorders (11) while aspirin, which inhibits prosta- glandin synthesis, is thought to cause tinnitus by increasing labyrinthine pressure (12). Therefore, tinnitus and Meniere's disease (labyrinthine hydrops) may be an auditory "glaucoma", another basal lamina transport-dependent fluid pressure disorder in an enclosed "tissue cell" resulting from disturbed PG and fatty acid metabolism. Both long term vision and hearing losses would then have similar mechanical causes.

9. The "Tissue Cell Theory of Metazoa" (9) suggests that glau- coma, tinnitus and Meniere's disease belong to a set of "baro- pathies" statistically involving all the closed "tissue cells" of the transport organ system and, therefore, also including articular Wglaucoma" (i.e., arthritis) and bursal "glaucoma" (i.e., bursitis). Various combinations of these may result de- pending on genetic predisposition and antigenic encounter. Picking a different reference disorder we may alternatively view all these as types of ocular, cochlera, vestibular and bursal "arthritis". Depending on neural innervation the symptoms then variously involve disorders of vision, hearing, balance or pain, respectively.

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CONCLUSIONS

Melatonin should be tried in glaucoma, tinnitus, vertigo, arthritis, bursitis and age dyspigmentation. One gram orally per day for one month in man has reduced certain forms of cutaneous hyperpigmentation (4). Topical application to the eye should in- volve no greater risk than that associated with current agents. Prostaglandins have also been applied in this way to lower intra- ocular pressure (2). The hormone prolactin has some of the lipid regulating effects of melatonin while the antipsychotic, clo- zapine, may induce prostaglandin synthesis (1). Horrobin (13) suggests that since colchicine may compete for the melatonin site and is far more stable, it may be more effective than melatonin itself.

To obtain any long term benefits from modified lipid meta- bolism the reactions controlled by the above agents should not be substrate limited. To this end supplements may be advisable in- cluding linoleic and linolenic (linseed oil) acid (up to 0.1-0.2 gm/kg/day), primrose oil (gamma linolenic acid), dihomo-gamma- linolenic acid (up to 0.2 mg/kg/day (14)) and arachidonic acid (1.0 mg/kg/day) all covered by 500 I.U. of tocopherol per day as antioxidant along with the essential trace elements, Zn, Cu and Se. Linseed oil, 15-30 cc/day, for 3 months has been accompanied in the case above by declining tinnitus and, surprisingly, by considerable age spot resorption.

The recent successful use of elemental diets for over one year (15) offers a way to test for allo-antigenic foods and also to assess the secondary role of alcohol and caffeine. Viral allo-antigens might require immunosuppressive therapy or inter- feron. Cross studies should be explored, e.g., carbonic anhy- drase inhibitors used in glaucoma should be tried in tinnitus.

Using the concept of a "Therapeutic Chain" we can summarize the treatment possibilities and their rationale for the various "baropathies" as designed to correct a putative prostaglandin deficiency: (1) augment PG by topical, i.v. or oral PG (Upjohn's Prostin) noting that oral PG has been used for years in the in- duction of human labor where it may also cause an incidental lowering of intraocular pressure (2); (2) activate PG synthetase noting that epinephrine derivatives now used may work in this way in glaucoma (2); (3) activate phospholipase A acid precursors by melatonin/colchicine, espe 8.

release of fatty ially to oppose any

abnormal cortisol inhibition at this point: (4) augment PGl,2 synthesis with oral safflower oil and PG3 synthesis with oral linseed oil: (5) augment antibodies by, say, oral passive im- munization using Meda-Milk, a new hyperimmunoglobulin dried milk product available free of charge for research from General Nutrition Corporation, Research Dept., Box 349, Fargo, N.D.; (6) remove possible antigen sources using interferon, elemental diets and a switch to high fiber diet which can shift colonic flora from anaerobic bacteroides to aerobic lactobaccilus and strep- tococcus which secondarily tends to normalize triglyceride and

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cholesterol metabolism (16) which should then also tend to nor- malize immune mechanisms: and, finally, (7) although not clini- cally feasible as yet attempt genetic correction when possible.

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