tretinoin and Myopia

To investigate the effect of short-wavelength light (SL) on guinea pigs with lens-induced myopia (LIM) and the possible retinoic acid (RA)-related mechanisms.. Two-week-old guinea pigs (n = 60) with monocular -5D lenses were reared under white light (WL, 580 lux) or SL (440 nm, 500 lux). The left eyes were uncovered as control. Refractive error (RE) and axial length (AL) were measured at baseline, one week, two weeks, and four weeks after intervention. Retinal RA was measured from four guinea pigs after two and four weeks of treatment with HPLC. Two-week-old guinea pigs (n = 52) with monocular -5D lens were fed with either RA or its synthesis inhibitor citral every third day in the morning, and half from each group were reared under WL or SL conditions. RE and AL were recorded at baseline and two and four weeks after intervention. Retinal RA was measured after four weeks of intervention.. At the end of treatment, guinea pigs exposed to SL were less myopic than to WL (2.06 ± 1.69D vs. -1.00 ± 1.88D), accompanied with shorter AL (P = 0.01) and less retinal RA (P = 0.02). SL reduced retinal RA even after exogenous RA supplementation (P = 0.02) and decelerated LIM compared to WL (1.66 ± 1.03D vs. -3.53 ± 0.90D). Citral slowed ocular growth, leading to similar RE in W+CI and S+CI groups (3.39 ± 1.65D vs. 5.25 ± 0.80D).. Overall, SL reduced LIM in guinea pigs, even in those supplemented with oral RA, accompanied by reduced retinal RA levels. Oral RA accelerated eye elongation, but citral equally decelerated eye elongation under SL and WL with no significant retinal RA reduction.

Topics: Animals; Axial Length, Eye; Biometry; Chromatography, High Pressure Liquid; Contact Lenses; Disease Models, Animal; Guinea Pigs; Light; Myopia; Refraction, Ocular; Retina; Retinoscopy; Tretinoin

By investigating that (i) all-trans retinoic acid (ATRA) affects human retinal pigment epithelium (RPE) in expressing and secreting transforming growth factor (TGF)-β. The RPE cell line (D407) was treated with (i) ATRA (10 μM), (ii) U73122 (5-40 μM) and ATRA (10 μM), or (iii) SQ22536 (5-40 μM) and ATRA (10 μM). The control group was no-treated. After stimulated at 2, 4, 8, 16, 24, and 48 h, The expression and secretion of TGF-β. TGF-β2 in the cytoplasm was time-dependent increased by ATRA (p < 0.001). A time-dependent increase in the TGF-β2 protein of the supernatant was induced by ATRA (p < 0.001). U73122 (in the range of 5 to 40 μM) could suppress the secretion of TGF-β2 induced by ATRA (p < 0.001), and 40 μM U73122 could completely inhibit the up-regulated effect of 10 μM ATRA. However, SQ22536 (in the range of 5 to 40 μM) had no impact on the secretion of TGF-β. In RPE cells, ATRA stimulates the secretion of TGF-β

Topics: Adenylyl Cyclases; Cells, Cultured; Cytoplasm; Epithelial Cells; Humans; Myopia; Retinal Pigment Epithelium; Signal Transduction; Transforming Growth Factor beta2; Tretinoin; Type C Phospholipases; Up-Regulation

To observe the role of all-trans retinoic acid (ATRA) during the similar myopia changes of cultured rabbit retinal pigment epithelium (RPE) cells, as well as the variation changes and relationships with myopic correlation factors such as hepatocyte growth factor (HGF) and matrix metalloprateinase-2 (MMP-2). Rabbit RPE cells of primary generation were selected and cultured to fifth generation by subculture. Then the morphology of RPE cells were observed and cell vitality was analyzed by using the Trypan blue reject test. The expressions of HGF and MMP-2 in RPE cells were tested by using an immunobistochemistry method. The HGF concentration in RPE cell culture fluid was detected by applying enzyme-linked immunosorbnent assay (ELISA). As the ATRA concentration enhanced and action time prolonged, the survival rate of RPE cells was reduced, but the expressions of HGF and MMP-2 increased, so did the secretion of HGF. ATRA concentration with no less than 5 nM/ml was able to induce the growth inhibition of RPE cells and the decrease in survival rate, which was similar to the changes in RPE cells in myopia. With the actin of ATRA, the expressions of HGF and MMP-2 increased in RPE cells, with more distinct in HGF increase.

Topics: Animals; Enzyme-Linked Immunosorbent Assay; Myopia; Rabbits; Retinal Pigment Epithelium; Tretinoin

Zonula occludens-1 (ZO-1) and occludin are important tight junction (TJ)-associated proteins, which are expressed in the retinal pigment epithelium (RPE)-choroid complex. Retinoic acid (RA) is a regulator of eye growth and may play an important role in forming functional TJs. The aim of this study was to detect the changes that occur in the expression of ZO-1 and occludin in the RPE-choroid complex of guinea pigs with lens-induced myopia (LIM), and to investigate the effect of RA on TJ-associated proteins in vivo. We developed an animal model of myopia by placing a -6.00 D negative lens on the right eyes of 3-week-old guinea pigs. The refractive error and axial length of the eye were measured on days 0, 3, 7 and 14. High-performance liquid chromatography (HPLC) was performed to detect the changes in endogenous RA in the RPE-choroid complex. The expression of ZO-1 and occludin was observed by immunofluorescence and assayed by western blot analysis. Additionally, 2 µl LE540 (2.5 µg/µl), an antagonist of RA receptors (RARs), was injected into the vitreous chamber of the eyes of guinea pigs with LIM and 2 µl phosphate-buffered saline (PBS) (2.5 µg/µl) were injected as a negative control. We observed no obvious change in RA, ZO-1 and occludin expression in the normal control group within 14 days. In the LIM and LIM plus PBS groups, the level of RA and the expression of ZO-1 and occludin in the RPE-choroid complex significantly increased within 14 days along with the development of myopia. However, the level of RA was inhibited and the expression of TJ-associated proteins decreased in the eyes of guinea pigs with LIM following the injection of LE540. Thus, we consider that the expression of ZO-1 and occludin is increased in the RPE-choroid complex during the development of myopia. This change in expression may be regulated by RA, a factor known to be involved in the regulation of eye growth.

Topics: Animals; Blotting, Western; Choroid; Disease Models, Animal; Fluorescent Antibody Technique; Guinea Pigs; Lens, Crystalline; Myopia; Refractometry; Retinal Pigment Epithelium; Tight Junction Proteins; Tight Junctions; Tretinoin; Vision, Ocular

To investigate the effect of all-trans retinoic acid (atRA) on the barrier function of myopia retinal pigment epithelium (RPE), primary RPE cells from guinea pigs were cultured on the filters as monolayer and treated with 10⁻⁹ M atRA. Epithelial permeability was measured by transepithelial electrical resistance (TER) and HRP concentration, western blot was used to observe the expression of intercellular junction-associated proteins. Treatment of primary cultures of confluent myopia RPE cells with atRA resulted in a progressive increase in TER and a progressive decrease of HRP concentration in the basolateral compartment. The expression of E-cadherin, Occludin and Claudin-1 proteins were up-regulated after treatment with atRA for 6h to 48 h. We concluded that atRA could promote the epithelial barrier function of myopia RPE monolayer possibly by regulating expression of intercellular junction-associated proteins.

Topics: Animals; Apoptosis; Cadherins; Cell Differentiation; Claudin-1; Guinea Pigs; Intercellular Adhesion Molecule-1; Intercellular Junctions; Myopia; Occludin; Permeability; Retinal Pigment Epithelium; Tretinoin; Zonula Occludens-1 Protein

All-trans-retinoic acid (atRA) has been implicated in the local regulation of scleral proteoglycan synthesis in vivo. The purpose of the present study was to identify the enzymes involved in the synthesis of atRA during visually guided ocular growth, the cells involved in modulation of atRA biosynthesis in the choroid, and the effect of choroid-derived atRA on scleral proteoglycan synthesis.. Myopia was induced in White leghorn chicks by form deprivation for 10 days, followed by up to 15 days of unrestricted vision (recovery). Expression of atRA synthesizing enzymes was evaluated by semiquantitative qRT-PCR, in situ hybridization, and immunohistochemistry. atRA synthesis was measured in organ cultures of isolated choroids using LC-tandem MS quantification. Scleral proteoglycan synthesis was measured in vitro by the incorporation of (35)SO(4) in CPC-precipitable glycosaminoglycans. RESULTS; RALDH2 was the predominant RALDH transcript in the choroid (> 100-fold that of RALDH3). RALDH2 mRNA was elevated after 12 and 24 hours of recovery (60% and 188%, respectively; P < 0.01). The atRA concentration was significantly higher in cultures of choroids from 24-hour to 15-day recovering eyes than in paired controls (-195%; P < 0.01). Choroid conditioned medium from recovering choroids inhibited proteoglycan synthesis to 43% of controls (P < 0.02, paired t-test; n = 16) and produced a relative inhibition corresponding to a RA concentration of 7.20 × 10(-8) M.. The results of this study suggest that RALDH2 is the major retinal dehydrogenase in the chick choroid and is responsible for increased atRA synthesis in response to myopic defocus.

Topics: Aldehyde Dehydrogenase; Animals; Blotting, Northern; Blotting, Western; Chickens; Choroid; Disease Models, Animal; In Situ Hybridization; Myopia; Proteoglycans; Retinal Dehydrogenase; Reverse Transcriptase Polymerase Chain Reaction; Sclera; Tretinoin

To determine the associations between corneal biomechanical parameters as measured by the Reichert Ocular Response Analyser (ORA) and disc morphology and retinal nerve fibre layer thickness (RNFL) measured by the Heidelberg Retinal Tomograph (HRT) II in Singaporean children.. This is a cross-sectional study conducted on a subset of children enrolled in the Singapore Cohort Study of the Risk Factors of Myopia (SCORM). Corneal hysteresis (CH), corneal resistance factor (CRF) and central corneal thickness (CCT) were measured with the ORA. Optic disc morphology and RNFL thickness were assessed by the HRT II. Cycloplegic refraction and ultrasound A-scans were also performed, and disc tilt was assayed from stereo photographs.. 102 subjects (mean age 12.01 (SD 0.57) years; range 11-14 years) were included in the study. The mean CH was 12.00 (1.40) mm Hg, the mean CRF was 11.99 (1.65) mm Hg, and the mean CCT was 581.12 (33.53) mum. Eyes with tilted discs had significantly longer axial lengths and more myopic refraction than eyes without tilted discs. There were no significant correlations between CH, CRF or CCT and the HRT II parameters, after the application of the Bonferroni correction. When stratified for disc tilt, however, the global disc area was significantly correlated with CCT (r = -0.49, p = 0.001).. Corneal biomechanical properties as measured with the ORA do not vary with optic disc parameters or RNFL. Central corneal thickness is correlated with disc area in Singaporean schoolchildren with tilted discs. This relationship may influence glaucoma risk in myopic subjects.

Topics: Adolescent; Biomechanical Phenomena; Child; Cornea; Corneal Diseases; Cross-Sectional Studies; Diagnostic Techniques, Ophthalmological; Female; Glaucoma; Humans; Intraocular Pressure; Male; Myopia; Nerve Fibers; Optic Disk; Refractive Errors; Singapore; Tretinoin

To explore the temporal expression of retinal-choroidal transforming growth factor-beta2 (TGF-beta2) in form-deprived myopia (FDM) chick eyes and study the effect of an inhibitor (disulfiram, DSF) of retinoid acid (RA) synthesis on refractive development and the expression of TGF-beta2.. Ninety new hatched white leghorn chicks were divided randomly and equally into 3 groups: unilateral occluded with frosted goggles (Group A); unilateral intravitreal injection of 4 mmol of the non-specific aldehydedehydrogenase inhibitor disulfiram with further treatment with goggles (Group B); unilateral intravitreal injections of 4 mmol of disulfiram without further treatment with goggles (Group C). Refraction and axial length were measured on 1, 7 and 14 days after treatment. Expression levels of TGF-beta2 and TGF-beta2 mRNA in the retinal-choroid layer were analyzed by immunohistochemistry and real-time RT-PCR.. In Group A, the form-deprived eyes made by goggles developed myopia (P<0.05 on day 1, P<0.01 on days 7 and 14, compared with the contralateral eyes) with a lengthening of the axial length (P<0.01 on days 7 and 14, compared with the contralateral eyes), as well as a lower level of TGF-beta2 expression (P<0.01 on days 7 and 14, compared with the contralateral eyes). In Groups B and C, there was no statistically significant difference in refraction and axial length between treated and contralateral eyes (P>0.05) with TGF-beta2 mRNA level growing on day 7 and decreased on day 14 in group B and decreased on day 1, increased on days 7 and 14 in Group C (P<0.01, compared with the contralateral eyes). Immunohistochemistry showed that the expression of TGF-beta2 was mainly changed in the outer part of photoreceptor layer and retinal pigment epithelium (RPE) layer.. TGF-beta2 mRNA level decreased in FDM eyes. Disulfiram can up-regulate the level of TGF-beta2 mRNA expression in the posterior retinal-choroid, and inhibit the elongation of axial length and refractive error made by frosted goggles as well. Disulfiram which inhibits the synthesis of retinoid acid may suppress deprivation myopia by up-regulating the expression level of TGF-beta2 mRNA.

Topics: Animals; Chickens; Disulfiram; Myopia; Random Allocation; Retina; RNA, Messenger; Sensory Deprivation; Transforming Growth Factor beta2; Tretinoin; Up-Regulation

It is generally accepted that the increase in choroidal thickness in response to myopic defocus in chicks acts to move the retina towards the image plane. It may also constitute part of the signal cascade in the visual regulation of eye growth. To test this, we used the nitric oxide synthase inhibitor l-NAME to inhibit the defocus induced choroidal thickening under two different visual conditions, and looked at the effects on ocular growth rate. Exp. 1: Deprivation/Vision: chicks were monocularly deprived of form vision with translucent diffusers from day 6 to day 9. In the middle of each day the diffusers were removed for 2 h. One group received an intravitreal injection of 30 microl l-NAME (16 micromole; n=12) prior to the vision, a second group received injections of physiological saline (n=11). Exp. 2: Recovery/Vision: chicks were made myopic by form deprivation from day 6 to day 10. On days 11 to 14 the diffusers were removed for 2 h per day for 4 days to allow eyes to "recover" from the myopia. One group received an injection of l-NAME prior to vision (n=8), the other saline (n=6). Refractive errors were measured with a refractometer at the start (days 6 and 11) and end (days 10 and 15, respectively) of both experiments. Ocular dimensions were measured with high frequency A-scan ultrasonography at the start and end, and on the third experimental day immediately before and after the period of vision. Choroidal retinoic acid synthesis was measured by HPLC. Finally, NO production and scleral proteoglycan synthesis were measured in eyes wearing positive lenses 6 and 24h after an injection of l-NAME. l-NAME prevented the transient vision-induced choroidal thickening in both experiments. Furthermore, l-NAME inhibited the protective effect of brief daily vision: eyes became significantly more myopic than saline controls (exp. 1: -9 D vs -2.7D; exp. 2: -0.9 D vs +4.3 D; p<0.005 for both) and grew faster (change in lens-sclera: exp. 1: 295 vs 158 microm; exp. 2: 147 vs 39 microm; p<0.05 for both). Notably, l-NAME inhibited the growth of the anterior chamber (exp. 1: 88 vs 185 microm; exp. 2: 147 vs 254 microm; p<0.01 for both). Injections of l-NAME after the periods of vision had no effect on growth at the back of the eye, but still had an inhibitory effect on the anterior chamber. Retinoic acid levels in the drug-injected choroids were significantly decreased compared to controls. In eyes responding to positive lenses, l-NAME inhibited NO synthesis and disi

Topics: Animals; Chickens; Choroid; Enzyme Inhibitors; Eye; Form Perception; Injections; Myopia; NG-Nitroarginine Methyl Ester; Nitric Oxide; Proteoglycans; Sclera; Tretinoin; Ultrasonography; Vitreous Body

The purpose of this study was to examine the possibility that all-trans-retinoic acid (RA) in the eye is a signal related to changes in scleral extracellular matrix in a primate model of postnatal eye growth.. Juvenile marmosets (Callithrix jacchus) were divided into two experimental groups based on their response to monocular deprivation with diffusers: group 1, treated eyes becoming longer than fellow control eyes (n = 8), and group 2, treated eyes becoming shorter than control eyes (n = 7). Eyes were enucleated, dissected, and assayed for changes in the rates of scleral glycosaminoglycan (GAG) synthesis and ocular RA synthesis. The rate of incorporation of (35)SO4 into CPC-precipitable GAG in scleras was taken as a measure of the rate of synthesis of proteoglycans. In the same eyes the rate of RA synthesis in vivo was measured separately in the retina and the choroid/RPE (choroid with RPE attached) by HPLC. The effect of RA on the rate of scleral GAG synthesis was also examined in tissue-cultured pieces of sclera from additional marmosets.. Induced changes in vitreous chamber length in diffuser-treated eyes correlated inversely with the rate of scleral GAG synthesis (P < 0.05) and directly correlated with the rate of RA synthesis measured separately in the retina (P < 0.05) and the choroid/RPE (P < 0.05). In group 1, the rate of scleral GAG synthesis was significantly lower (P < 0.01) in the treated eyes relative to control eyes, and the rate of RA synthesis in both the retina and the choroid/RPE was significantly higher (P < 0.01). In group 2, the rates of scleral GAG synthesis and RA synthesis in either the retina or choroid/RPE were not found to change significantly in the treated eyes compared with the control eyes. RA partially reduces the rate of scleral GAG synthesis in tissue-cultured primate sclera in a dose-dependent manner after several days.. RA may play a role in the visual control of postnatal eye growth in primates, possibly by inducing changes in scleral extracellular matrix associated with increasing eye size. Decreasing growth rate below control levels may involve other mechanisms.

Topics: Animals; Callithrix; Choroid; Chromatography, High Pressure Liquid; Disease Models, Animal; DNA; Extracellular Matrix; Eye; Glycosaminoglycans; Myopia; Organ Culture Techniques; Retina; Sclera; Sensory Deprivation; Tretinoin; Vitreous Body

A growing eye becomes myopic after form deprivation (FD) or compensates for the power and sign of imposed spectacle lenses. A possible mediator of the underlying growth changes is all-trans retinoic acid (RA). Eye elongation and refractive error (RE) was manipulated by raising guinea pigs with FD, or a spectacle lens worn on one eye. We found retinal-RA increased in myopic eyes with accelerated elongation and was lower in eyes with inhibited elongation. RA levels in the choroid/sclera combined mirrored these directional changes. Feeding RA (25 mg/kg) repeatedly to guinea pigs, also resulted in rapid eye elongation (up to 5 times normal), and yet the RE was not effected. In conclusion, RA may act as a signal for the direction of ocular growth.

Topics: Administration, Oral; Animals; Eye; Guinea Pigs; Models, Animal; Myopia; Refractive Errors; Tretinoin; Vision, Ocular

Eye growth is visually regulated via messengers that are released from the retina. The retina involves a yet unknown algorithm to analyse the projected image so that the appropriate growth rates for the back of the eye are ensured. One biochemical candidate that could act as a growth controller, is retinoic acid (RA). Previous work (Seko, Shimokawa and Tokoro, 1996; Mertz et al., 1999) has shown that retinal and choroidal RA levels are indeed predictably changed by visual conditions that cause myopia or hyperopia, respectively. We have studied in which fundal tissues aldehyde dehydrogenase-2 (AHD2) and retinaldehyde dehydrogenase-2 (RALDH2), enzymes involved in RA synthesis, are expressed and at which levels the effects of vision on RA levels may be controlled. Using Northern blot analysis, we have found that the retinal mRNA level of the AHD2 is up-regulated after 3 days of treatment with negative lenses (negative lenses place the image behind the retina). The abundance of the retinal mRNA of a RA receptor, RAR-beta, was up-regulated already after 6 hr of treatment with positive lenses (positive lenses place the image in front of the retina). The up-regulation persisted for at least 1 week. Finally, we have studied the effects of an inhibitor of RA synthesis, disulfiram, on the visual control of eye growth. We found inhibition of myopia as induced by frosted goggles ('deprivation myopia') but no significant inhibitory effects on refractive errors induced by +7D or -7D lenses. Our results are in line with the hypothesis that RA may play a role in the visual control of eye growth. The RA system differs from a number of other candidates (dopamine, cholinergic agents, opiates) in that it distinguishes between positive and negative defocus, similar to the immediate early gene ZENK (Stell et al., 1999). The exact time kinetics of the changes have still to be worked out since it is possible that the changes in RA relate to already occurring changes in growth rather than to initial steps of the signaling cascade.

Topics: Age Factors; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Aldehyde Oxidoreductases; Animals; Blotting, Northern; Chickens; Choroid; Eyeglasses; Myopia; Pigment Epithelium of Eye; Receptors, Retinoic Acid; Retina; Retinal Dehydrogenase; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sclera; Signal Transduction; Tretinoin; Vision, Ocular

Research over the past two decades has shown that the growth of young eyes is guided by vision. If near- or far-sightedness is artificially imposed by spectacle lenses, eyes of primates and chicks compensate by changing their rate of elongation, thereby growing back to the pre-lens optical condition. Little is known about what chemical signals might mediate between visual effects on the retina and alterations of eye growth. We present five findings that point to choroidal retinoic acid possibly being such a mediator. First, the chick choroid can convert retinol into all-trans-retinoic acid at the rate of 11 +/- 3 pmoles mg protein(-1) hr(-1), compared to 1.3 +/- 0.3 for retina/RPE and no conversion for sclera. Second, those visual conditions that cause increased rates of ocular elongation (diffusers or negative lens wear) produce a sharp decrease in all-trans-retinoic acid synthesis to levels barely detectable with our assay. In contrast, visual conditions which result in decreased rates of ocular elongation (recovery from diffusers or positive lens wear) produce a four- to five-fold increase in the formation of all-trans-retinoic acid. Third, the choroidal retinoic acid is found bound to a 28-32 kD protein. Fourth, a large fraction of the choroidal retinoic acid synthesized in culture is found in a nucleus-enriched fraction of sclera. Finally, application of retinoic acid to cultured sclera at physiological concentrations produced an inhibition of proteoglycan production (as assessed by measuring sulfate incorporation) with a EC50 of 8 x 10(-7) M. These results show that the synthesis of choroidal retinoic acid is modulated by those visual manipulations that influence ocular elongation and that this retinoic acid may reach the sclera in concentrations adequate to modulate scleral proteoglycan formation.

Topics: Animals; Annexins; Cell Nucleus; Cells, Cultured; Chickens; Choroid; Eyeglasses; Hyperopia; Myopia; Protein Binding; Proteoglycans; Refractive Errors; Retina; Sclera; Tretinoin

We previously reported that expression of retinoic acid receptor beta increases in the sclera of the 2-week-old chick with form deprivation myopia (FDM) and that all-trans-retinoic acid (t-RA) influences proliferation and differentiation of scleral cells. The purpose of this study was to quantify t-RA in the retina of the chick with FDM and to investigate the role of t-RA in FDM in the chick. FDM was induced in 2-day-old chicks by placement of a translucent plastic goggle over one eye, with the contralateral eye used as a control. After 5 days, the chicks were sacrificed. t-RA was extracted from neural retina and served for high-performance liquid chromatography analysis. 3H-t-RA was used for normalization. Pieces of the retinae from 5 eyes served as one sample. As a result, t-RA was 09.60 +/- 0.86 ng/eye (0.387 +/- 0.056 ng/mg protein) in the myopic retina was significantly higher than that in the control (p < 0.05, n = 7). These results demonstrate that t-RA increases in the retina within 5 days after visual deprivation. This finding suggests that t-RA may play a role in the metabolic changes in FDM.

Topics: Animals; Animals, Newborn; Chickens; Chromatography, High Pressure Liquid; Male; Myopia; Retina; Sensory Deprivation; Tretinoin; Vision, Monocular

The purpose of this study is to clarify the role of retinoic acid (RA) in the mechanism of form-deprivation myopia (FDM) in the chick. FDM was induced in two-day old chicks by placement of a translucent plastic goggle over one eye, with the contralateral eye used as a control. After 12 days, the chicks were euthanized. RNA was extracted from scleras in the posterior segments, transcribed into cDNA, and amplified by PCR with primers specific for retinoic acid receptor (RAR) beta. G3PDH was used as a reference gene for normalization. The effects of RA, with or without TGF-beta, on the proliferation of scleral chondrocytes and scleral fibroblasts from 17-day chick embryos were studied by use of a colorimetric assay, and the alkaline phosphatase activities of those cells also studied. Furthermore, RAR beta expression in response to RA in cultured scleral cells was studied. As a result, RT-PCR products of the expected sizes were obtained from scleras from the myopic and control eyes. Expression of RAR beta in the myopic scleras was significantly higher than that in the controls. The proliferation of scleral chondrocytes and scleral fibroblasts was inhibited by treatment with RA in a dose-dependent manner (in 10% FBS). In the presence of TGF-beta (in 0.5% FBS), RA treatment stimulated the proliferation of scleral chondrocytes but inhibited the proliferation of scleral fibroblasts. RA induced alkaline phosphatase activities in both the scleral chondrocytes and scleral fibroblasts. RAR beta expression was induced by RA in cultured scleral cells. These results demonstrate that RA appears to play a role in the mechanism of FDM in the chick. However, it is also possible that the changes in the expression of RAR beta were secondary events related to other mechanisms responsible for ocular enlargement.

Topics: Alkaline Phosphatase; Animals; Cell Culture Techniques; Cell Division; Chickens; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Male; Myopia; Polymerase Chain Reaction; Receptors, Retinoic Acid; Sclera; Sensory Deprivation; Transforming Growth Factor beta; Tretinoin

A patient developed transient, acute myopia while on isotretinoin (Accutane) therapy for acne. This idiosynactic adverse reaction has not been previously described. There was a clear relationship between restarting the Accutane and recurrence of the transient myopia.

Topics: Acne Vulgaris; Acute Disease; Adult; Female; Humans; Isotretinoin; Myopia; Tretinoin