tretinoin and Cataract

Normal anterior segment embryogenesis is summarized followed by a review of syndromes of spontaneous and inherited conditions of abnormal development in humans and animals. The study of teratogen-induced malformations in animal models has provided valuable information about critical periods during gestation for the initiation of anterior segment dysgenesis. Although the major developmental events leading to iridocorneal angle formation occur during the third trimester, it appears that embryonic insult much earlier in human gestation (during the first three to five weeks post fertilization) can induce an abnormal sequence of events leading to anterior segment dysgenesis.

Topics: Abnormalities, Drug-Induced; Animals; Anterior Eye Segment; Cataract; Disease Models, Animal; Ethanol; Female; Glaucoma; Humans; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Ochratoxins; Pregnancy; Syndrome; Teratogens; Trabecular Meshwork; Tretinoin

Thirty patients with treatment-resistant cystic and conglobulate acne entered a randomized double-blind protocol, testing the efficacy of isotretinoin versus tetracycline. After 16 weeks of isotretinoin treatment, the mean number of cysts decreased by 64% and the mean sum of the longest diameters was reduced by 68%. After 16 weeks of tetracycline therapy, the total number of cysts showed a mean decrease of 52%, and the mean sum of the longest diameters decreased by 60%. The reduction in the number of cysts and the sum of their longest diameters that occurred after 16 weeks of treatment was statistically significant for each of the treatment groups, but there was no statistically significant difference between the treatment groups at the end of therapy. Eight weeks after the discontinuation of treatment in the isotretinoin group, there was an overall reduction from baseline of 82% in the cyst count and 88% in the sum of the longest diameters. In the tetracycline treatment group, the overall reduction from baseline in the cyst count was 54% and in the sum of the longest diameters, 60%. This led to a statistically significant difference in the two treatment groups at 24 weeks. All patients on isotretinoin experienced side effects that were primarily related to the integumentary system but necessitated discontinuation of the drug for a short period of time in only one patient. Long-term follow-up, 8 months after discontinuation of the study, showed a prolonged significant remission of acne in the isotretinoin group but not in the tetracycline group.

Topics: Acne Vulgaris; Adolescent; Adult; Cataract; Cheilitis; Clinical Trials as Topic; Double-Blind Method; Epistaxis; Female; Follow-Up Studies; Humans; Isomerism; Isotretinoin; Male; Random Allocation; Tetracycline; Tretinoin; Xerophthalmia; Xerostomia

To determine whether retinoic acid (RA)-mediated inhibition of deregulated calpains had any effect on the development of cataract given that accumulating evidence has demonstrated a possible relationship between cataractogenesis and inappropriate activation of calpains.. The authors examined for Ca(2+) influx and expression alteration of calpains in F9 cells with or without RAs, such as all-trans retinoic acid (ATRA), and specific stimulant of retinoic acid receptor alpha (RARalpha; Am580) in the presence of oxidative stress, such as mediated by H(2)O(2). They next examined the clinical relevance of RAs by applying these agents to a murine diabetic cataract and observed the development of the disease.. F9 cells constitute a well-established autonomous cell model for investigating retinoid signaling, partially representing the lens epithelial phenotype, as determined by the expression of aquaporin 0, a specific differentiation marker for lens cells. Treatment with ATRA and Am580 significantly decreased the influx of Ca(2+) into the cells, causally resulting in decreased mRNA expression and inhibited activation of calpains. In addition, RARalpha agonists significantly abrogated the upregulation of calpain 2 induced by H(2)O(2), which is a potential etiological contributor to the diabetic cataract, whereas H(2)O(2) had no effect on calpain 1. Importantly, this RA-mediated gene-expression alteration was sufficient for dramatically inhibiting the development of lens opacity in mice with diabetes.. Results showed that a certain type of RA inhibits Ca(2+) elevation and subsequent overactivation of calpains, suggesting the potential feasibility of calpain-targeting therapies mediated by RA for cataract.

Topics: Animals; Benzoates; Calcium; Calpain; Cataract; Diabetes Mellitus, Experimental; Hydrogen Peroxide; Lens, Crystalline; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Receptors, Retinoic Acid; Retinoic Acid Receptor alpha; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tetrahydronaphthalenes; Tretinoin

Our aim was to evaluate the effect of an intraoperative single dose of retinoic acid (RA) or mitomycin C (MMC) in preventing posterior capsule opacification (PCO).. Twenty-seven rabbits were divided randomly into three groups. RA (250 microg/ml) and MMC (0.04 mg/ml) were given 0.1 ml by hydrosection and 0.9 ml into the capsular bag after phacoemulsification. The third group served as a control group. Three months after intervention PCO was graded clinically. Furthermore, proliferation of lens epithelial cells was evaluated histologically.. Two eyes developed corneal edema in the MMC group. On clinical assessment, RA and MMC were significantly effective in preventing PCO compared with controls (P<0.005). On histological analysis, there was significantly reduced proliferative activity on posterior capsules in the treatment groups, in contrast to multilayer cells in the control group.. Intraoperative single-dose administration of RA and MMC significantly prevented the development of PCO in rabbit eyes. The optimal biocompatible dosage must be carefully determined by further investigation.

Topics: Animals; Antimetabolites; Cataract; Cell Division; Epithelial Cells; Intraoperative Period; Lens Capsule, Crystalline; Mitomycin; Ophthalmic Solutions; Phacoemulsification; Rabbits; Random Allocation; Tretinoin

All-trans retinoic acid, a metabolite of retinol, is a possible morphogen in vertebrate development. Two classes of cellular proteins, which specifically bind all-trans retinoic acid, are thought to mediate its action: the nuclear retinoic acid receptors (RAR alpha, beta, gamma), and the cytoplasmic binding proteins known as cellular retinoic acid-binding proteins I and II (CRABP I and II). The function of the retinoic acid receptors is to regulate gene transcription by binding to DNA in conjunction with the nuclear retinoid X receptors (RXR alpha, beta, gamma), which in turn have 9-cis retinoic acid as a ligand. Several lines of evidence suggest that the role of the cellular retinoic acid-binding proteins is to control the concentration of free retinoic acid reaching the nucleus in a given cell. Here, we have addressed the role of the cellular retinoic acid-binding protein I in development by ectopically expressing it in the mouse lens, under the control of the alpha A-crystallin promoter. We show that this ectopic expression interferes with the development of the lens and with the differentiation of the secondary lens fiber cells, causing cataract formation. These results suggest that correct regulation of intracellular retinoic acid concentration is required for normal eye development. In addition, the generated transgenic mice also present expression of the transgene in the pancreas and develop pancreatic carcinomas, suggesting that overexpression of the cellular retinoic acid-binding protein is the cause of the tumors. These results taken together provide evidence for a role of the cellular retinoic acid-binding protein in development and cell differentiation. The relevance of these findings to the possible role of the cellular retinoic acid-binding proteins in the transduction of the retinoic acid signal is discussed.

Topics: Animals; Blotting, Northern; Cataract; Cell Differentiation; Gene Expression; In Situ Hybridization; Lens, Crystalline; Mice; Mice, Transgenic; Morphogenesis; Pancreatic Neoplasms; Receptors, Retinoic Acid; Tretinoin

Retinoic acid receptors (RARs) modulate gene expression following association with retinoic acid (RA). In transient transfection, an RAR alpha-beta-galactosidase fusion protein (RAR-LacZ) was able to transactivate expression in the absence of RA. When expressed in the ocular lens of transgenic mice, this constitutively active RAR-LacZ fusion gene resulted in founder and progeny animals that exhibited cataracts and microphthalmia, both being characteristics of retinoid-induced teratogenesis. The transgenic phenotypes indicate that retinoid teratogenesis can be mimicked by expression of a constitutively active RAR-LacZ fusion protein in retinoid-sensitive tissues.

Topics: Animals; Base Sequence; Carrier Proteins; Cataract; Gene Expression; Lac Operon; Lens, Crystalline; Mice; Mice, Transgenic; Microphthalmos; Molecular Sequence Data; Receptors, Retinoic Acid; Recombinant Fusion Proteins; Trans-Activators; Tretinoin

Topics: Acne Vulgaris; Cataract; Humans; Isotretinoin; Male; Middle Aged; Tretinoin

A total of 261 adverse ocular reactions occurred in 237 patients who received isotretinoin, a commonly used drug in the treatment of severe cystic acne. Blepharoconjunctivitis, subjective complaints of dry eyes, blurred vision, contact lens intolerance, and photodermatitis are reversible side effects. More serious ocular adverse reactions include papilledema, pseudotumor cerebri, and white or gray subepithelial corneal opacities; all of these are reversible if the drug is discontinued. Reported cases of decreased dark adaptation are under investigation. Isotretinoin is contraindicated in pregnancy because of the many reported congenital abnormalities after maternal use (including microphthalmos, orbital hypertelorism, and optic nerve hypoplasia).

Topics: Acne Vulgaris; Cataract; Conjunctivitis; Cysts; Eye; Eye Diseases; Eyelid Diseases; Humans; Inflammation; Isotretinoin; Photosensitivity Disorders; Skin Diseases; Tretinoin; Vision Disorders