No abstract

ABSTRACT.Purpose: Previous research has demonstrated that sex steroids exert a significant influence on the structure and function of numerous ocular tissues. To begin to explore the underlying basis of this hormone action, we examined whether various anterior and posterior tissues of the eye contain androgen, estrogen and progesterone receptor mRNAs. Methods: Tissue samples were obtained from adult male and female rats, rabbits and humans, processed for the isolation of total RNA and analyzed by RT-PCR, agarose gel electrophoresis and Southern blot hybridization. All PCR amplifications included positive and negative controls. Results: Our findings showed that androgen, estrogen and/or progesterone receptor mRNAs are present in the lacrimal gland, lacrimal gland acinar epithelial cells, meibomian gland, lid, palpebral and bulbar conjunctivae, cornea, iris/ciliary body, lens, retina/uvea, retina/choroid and retinal pigment epithelial cells of rats, rabbits or humans.Conclusions: Our findings demonstrate that sex steroid receptor mRNAs exist in a variety of ocular tissues and suggest that these sites may represent target organs for androgens, estrogens and/or progestins.

No abstract

Background/aims-Androgens have been reported to influence the structural organisation, functional activity, and/or pathological features of many ocular tissues. In addition, these hormones have been proposed as a topical therapy for such conditions as dry eye syndromes, corneal wound healing, and high intraocular pressure. To advance our understanding of androgen action in the eye, the purpose of the present study was twofold: firstly, to determine whether tissues of the anterior and posterior segments contain androgen receptor protein, which might make them susceptible to hormone eVects following topical application; and, secondly, to examine whether these tissues contain the mRNA for types 1 and/or 2 5 -reductase, an enzyme that converts testosterone to the very potent metabolite, dihydrotestosterone. During the past several decades, it has become quite apparent that androgens exert a significant influence on the structural organisation, functional activity, and/or pathological features of many ocular tissues, including the lacrimal gland, meibomian gland, conjunctiva, cornea, lens, uvea, and/or retina. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] The nature of this hormone action appears to involve the regulation of such ocular factors as glandular morphology, gene expression, protein synthesis and secretion, lipid production, tear film stability, immune function, epithelial cell mitosis, aqueous outflow pathway characteristics, intraocular pressure, and vascular permeability. Methods-Human1-5 10 13-16 In addition, androgens have been proposed as a topical therapy for such conditions as aqueous deficient and evaporative dry eye syndromes, corneal wound healing, and glaucoma. However, despite these findings, very little information exists concerning the precise target cells for androgen action, the specific ocular processes controlled by these hormones, or the mechanisms underlying androgen-eye interactions in humans.The mechanism(s) by which androgens act on the human eye most likely involves the local, intracrine synthesis of these hormones from adrenal sex steroid precursors (that is, dehydroepiandrosterone (DHEA) and DHEA sulphate (DHEA-S)) and a consequent androgen association with saturable, high aYnity, and steroid specific receptors in ocular tissues. 19The rationale for this hypothesis is twofold. Firstly, a large proportion of androgens in men, and the majority of these hormones in women, are produced in peripheral tissues from adrenal precursors. 18 In fact, humans and primates are unique in possessing adrenal glands that secrete large amounts of DHEA and DHEA-S, which are then converted into potent androgens and oestrogens by steroidogenic enzymes in peripheral sites and thereby permit target tissues to adjust the formation and metabolism of sex steroids to local requirements. 18 20 Secondly, androgen receptors, which are members of the steroid/thyroid hormone/retinoic acid family of ligand activated transcription factors, appear to mediate almost all of the "classic" actions ...

PurposeThis study compares signs, symptoms and predictive tools used to diagnose dry eye disease (DED) and ocular surface disorders in six systemic well-defined and non-overlapping diseases. It is well known that these tests are problematic because of a lack of agreement between them in identifying these conditions. Accordingly, we provide here a comparative clinical profile analysis of these different diseases.MethodsA spontaneous and continuous sample of patients with Sjögren's syndrome (SS) (n = 27), graft-versus-host-disease (GVHD) (n = 28), Graves orbitopathy (n = 28), facial palsy (n = 8), diabetes mellitus without proliferative retinopathy (n = 14) and glaucoma who chronically received topical drugs preserved with benzalkonium chloride (n = 20) were enrolled. Evaluation consisted of a comprehensive protocol encompassing: (1) structured questionnaire - Ocular Surface Disease Index (OSDI); (2) tear osmolarity (TearLab Osmolarity System - Ocusense); (3) tear film break-up time (TBUT); (4) fluorescein and lissamine green staining; (5) Schirmer test and (6) severity grading.ResultsOne hundred and twenty five patients (aged 48.8 years-old±14.1, male:female ratio = 0.4) were enrolled in the study, along with 24 age and gender matched controls. Higher scores on DED tests were obtained in Sjögren Syndrome (P<0.05), except for tear film osmolarity that was higher in diabetics (P<0.001) and fluorescein staining, that was higher in facial palsy (P<0.001). TFBUT and OSDI correlated better with other tests. The best combination of diagnostic tests for DED was OSDI, TBUT and Schirmer test (sensitivity 100%, specificity 95% and accuracy 99.3%).ConclusionsDED diagnostic test results present a broad range of variability among different conditions. Vital stainings and TBUT correlated best with one another whereas the best test combination to detect DED was: OSDI/TBUT/Schirmer.

The afferent nerves of the cornea and conjunctiva, efferent nerves of the lacrimal gland, and the lacrimal gland are a functional unit that works cooperatively to produce the aqueous component of tears. A decrease in the lacrimal gland secretory function can lead to dry eye disease. Because aging is a risk factor for dry eye disease, study of the changes in the function of the lacrimal gland functional unit with age is important for developing treatments to prevent dry eye disease. No one mechanism is known to induce the changes that occur with aging, although multiple different mechanisms have been associated with aging. These fall into two theoretical categories: programmed theories of aging (immunological, genetic, apoptotic, and neuroendocrine) and error theories of aging (protein alteration, somatic mutation, etc). Lacrimal glands undergo structural and functional alteration with increasing age. In mouse models of aging, it has been shown that neural stimulation of protein secretion is an early target of aging, accompanied by an increase in mast cells and lipofuscin accumulation. Hyperglycemia and increased lymphocytic infiltration can contribute to this loss of function at older ages. These findings suggest that an increase in oxidative stress may play a role in the loss of lacrimal gland function with age. For the afferent and efferent neural components of the lacrimal gland functional unit, immune or inflammatory mediated decrease in nerve function could contribute to loss of lacrimal gland secretion with age. More research in this area is critically needed.

Summary:Two cases of GVHD with severe dry eyes are reported where conventional therapy failed to control ocular signs and symptoms. Autologous serum tears, however, resulted in a beneficial clinical effect with marked attenuation of the symptoms. This therapy proved to be safe during 10 months of treatment. Bone Marrow Transplantation (2000) 25, 1101-1103. Keywords: GVHD; dry eye; autologous serum tears; allogeneic PBPC transplantation The treatment of ocular disorders with biological fluids has long been advocated. 1 More recently, autologous serum (AS) tears have been indicated for the treatment of dry eye in Sjögren's syndrome. The rationale for this is based upon the fact that vitamins and growth factors present in tears are also present in serum. 2,3 In this report, we describe the treatment of dry eyes with AS tears in two adult women with extensive chronic graft-versus-host disease (GVHD) following allogeneic peripheral blood progenitor cell transplantation (PBPCT). Case 1A 44-year-old woman underwent PBPCT for chronic myeloid leukemia (CML) in the first chronic phase and developed sicca syndrome along with extensive chronic GVHD. Her previous ophthalmic history included only spectacles for myopia. The GVHD was treated with cyclosporin A and prednisone systemically and with commercial artificial tears, including preservative-free tears for 6 months, with minimal improvement in the ocular symptoms which included the sensation of presence of a foreign body, and redness.Examination revealed a corrected visual acuity of 20/25 for both eyes, conjunctival hyperemia and severe punctate At this point, we introduced AS tears, prepared as previously described, 2 with instructions to keep the bottles in a refrigerator and apply the drops several times a day. Four weeks later, the patient returned and reported an improvement in her symptoms from the day she started using the preparation. Compared to her previous tear substitute, the effect of AS tears lasted longer, allowing her to apply fewer drops throughout the day and also provided considerably more comfort in the morning, which was the most critical part of the day. Examination of her eyes showed a dramatic improvement in punctate staining, a reduction in hyperemia

No abstract