Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Retinoids”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources
PubMed1994

Solid tumours--chemoprevention with retinoids.

There is a clear change in the treatment strategies for solid tumours towards the treatment of early rather than advanced disease. Retinoids represent a potentially useful class of drugs in chemoprevention. Preclinical data and clinical experience suggests that different retinoids may have different spectra of antitumour activity and synergistic interactions between retinoids and cytokines have also been reported. 13-cis retinoic acid has shown some promising activity in preventing the onset of second primary tumours in head and neck cancer and fenretinide is being tested in the prevention of second primary breast cancers. An understanding of the role of the different retinoid receptors could lead to the design of compounds with a better therapeutic index. Despite these early indications that retinoids could be useful in this area, the development of such drugs is far from easy. Appropriate study designs for screening differentiating agents in the clinic, and the relevance of preclinical models of chemoprevention are challenges to be addressed. Unresolved issues include optimal patient selection, long clinical trial times, optimal dose, schedule and treatment duration. The use of biological surrogate markers for longer time-dependent trial endpoints could significantly contribute to more rapid development. Ongoing clinical studies, particularly in tobacco-related diseases, will better define the role of retinoids in this clinical setting. Clinicians should be encouraged to enter patients into large well organized clinical studies.

Antineoplastic Agents↗
PubMed1994

Retinoids suppress proliferation, induce cell spreading, and up-regulate connexin43 expression only in postconfluent 10T1/2 cells: implications for the role of gap junctional communication.

The antiproliferative actions of retinoids in the C3H/10T1/2 cell system are exhibited as a decrease in proliferation rate and a decreased cell saturation density at confluence. These actions correlate with up-regulated gap junctional communication (GJC) driven by the retinoid-induced increased expression of the gap junctional protein connexin43 (Cx43). Here we examine which actions of retinoids occur only in cells making extensive intercellular contacts, and thus may be mediated through GJC, and which are exhibited in the absence of extensive intercellular contacts and thus may be independent of GJC. In confluent cultures, the synthetic retinoid tetrahydrotetramethylnapthalenyl-propenylbenzoic acid (TTNPB) increased GJC, reduced the already low [3H]thymidine-labeling index of G1 growth-arrested confluent cells from 4.2 to < 0.1%, and increased the area occupied by each cell by 42%. In contrast, none of these parameters was altered in logarithmic growth phase cells with very limited intercellular contacts. In order to separate cell-cell contact from cell cycle-related phenomena, non-contacting cells were arrested in early G1 by lovastatin. In this situation, Cx43 expression was low and inducible by retinoids, as in G1/G0 growth-arrested confluent cells; however, no cell spreading was induced by TTNPB. In contrast, in non-contacting cycling cells or in cells arrested by aphidicolin, Cx43 expression was higher than in confluent cells. In this situation, TTNPB did not induce Cx43 and did not induce spreading. These data demonstrate the cell cycle phase dependence of connexin43 expression and of retinoid action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Solid tumours--chemoprevention with retinoids.

There is a clear change in the treatment strategies for solid tumours towards the treatment of early rather than advanced disease. Retinoids represent a potentially useful class of drugs in chemoprevention. Preclinical data and clinical experience suggests that different retinoids may have different spectra of antitumour activity and synergistic interactions between retinoids and cytokines have also been reported. 13-cis retinoic acid has shown some promising activity in preventing the onset of second primary tumours in head and neck cancer and fenretinide is being tested in the prevention of second primary breast cancers. An understanding fo the role of the different retinoid receptors could lead to the design of compounds with a better therapeutic index. Despite these early indications that retinoids could be useful in this area, the development of such drugs is far from easy. Appropriate study designs for screening differentiating agents in the clinic, and the relevance of preclinical models of chemoprevention are challenges to be addressed. Unresolved issues include optimal patient selection, long clinical trial times, optimal dose, schedule and treatment duration. The use of biological surrogate markers for longer time-dependent trial endpoints could significantly contribute to more rapid development. Ongoing clinical studies, particularly in tobacco-related diseases, will better define the role of retinoids in this clinical setting. Clinicians should be encouraged to enter patients into large well organized clinical studies.

Breast Neoplasms↗
PubMed1993

Retinoid effects in purified cultures of chick embryo retina neurons and photoreceptors.

PURPOSE: To investigate the effects of retinoic acid, retinol, and 11-cis retinaldehyde on proliferation, differentiation, and survival of cultured embryonic chick neural retina cells; to describe the metabolic transformations of these retinoids by the cultured cells. METHODS: Retinoids were added to glia-free, low-density cultures of neural retina cells, which underwent subsequent examination to determine the numbers of neurons and photoreceptors that differentiated and survived under differing conditions. Cells and conditioned medium were extracted to identify and quantify retinoid metabolic products by high pressure liquid chromatography. RESULTS: Retinoid treatment resulted in dose-dependent increases in the number of differentiated photoreceptors present in the cultures after 6 days; smaller increases in nonphotoreceptor neurons were also observed. Retinoids were more effective when added at culture onset than at later times, but they did not stimulate cell proliferation. The order of potency was retinol > 11-cis retinaldehyde > retinoic acid. Exogenous retinoic acid was recovered unmodified after a 24-hr incubation period; retinol was also stable and unmetabolized, except for the formation of a small quantity of retinyl acetate. 11-cis retinaldehyde was less stable, and was metabolized into both retinoic acid and retinol. CONCLUSIONS: Retinol, 11-cis retinaldehyde, and retinoic acid can promote the survival (and possibly differentiation) of cultured embryonic retina neurons and photoreceptors in the absence of glia and retinal pigment epithelium. Although retinoic acid is likely to function by interacting with one of the known nuclear receptors for this retinoid, the effectiveness of retinol in the absence of metabolic transformation into retinoic acid suggests the possible existence of a distinct, yet undiscovered receptor.

Animals↗
PubMed1996

Activation of retinoid receptors RAR alpha and RXR alpha induces differentiation and apoptosis, respectively, in HL-60 cells.

Induction of granulocytic differentiation in HL-60 myeloid leukemia cells by retinoids is followed by their death via apoptosis. Retinoids are known to mediate their biological effects through at least two distinct types of nuclear receptors, the retinoic acid receptors and retinoid X receptors. We undertook to characterize the potential role of these receptors in inducing differentiation and apoptosis by retinoids. For this, we used a previously described variant of an HL-60 cell line (HL-60R) in which retinoid receptor function has been abrogated due to a trans-dominant negative mutation. Retroviral vector-mediated gene transfer was used to introduce the normal retinoic acid receptor (RAR alpha) or retinoid X receptor (RXR alpha) into HL-60R cells. Our results suggest that ligand-induced activation of RAR alpha is sufficient to induce differentiation in HL-60 cells, whereas activation of RXR alpha can induce direct apoptosis of these cells without their prior commitment to differentiate.

ADP-ribosyl Cyclase↗
PubMed1997

Retinoids suppress epidermal growth factor-induced transcription of cyclooxygenase-2 in human oral squamous carcinoma cells.

Cyclooxygenase-2 (Cox-2), the inducible form of cyclooxygenase, is up-regulated in tumors and transformed cells. Because this enzyme catalyzes the formation of prostaglandins from arachidonic acid, chemopreventive strategies that suppress its expression could be useful for preventing cancer. We investigated whether retinoids suppressed basal expression of Cox-2 or EGF-mediated induction of Cox-2 in human oral squamous carcinoma cells. Treatment with retinoids [all-trans-retinoic acid (all-trans-RA), 9-cis-RA, 13-cis-RA, and retinyl acetate] suppressed both basal levels of Cox-2 and EGF-mediated induction of Cox-2 protein and synthesis of prostaglandin E2. Retinoids also suppressed the induction of Cox-2 mRNA by EGF. Transient transfection experiments showed that EGF caused about a 100% increase in Cox-2 promoter activity, an effect that was suppressed by retinoids. Levels of epidermal growth factor receptor were unaffected by retinoids. Epidermal growth factor caused a nearly 10-fold increase in mitogen-activated protein kinase activity; this effect was not blocked by retinoids.

Carcinoma, Squamous Cell↗
PubMed1997

[Retinoids: use in combating cancer].

Retinoids are a group of natural and synthetic analogues of vitamin A (retinol). The biological activity of retinoids is mediated by multiple nuclear receptors which bind to specific DNA sequences and regulate transcription of target genes. Retinoids affect cell growth and differentiation. Retinoids inhibit chemically induced carcinogenesis in experimental animals. Clinical application of retinoids is efficacious to different degrees in prevention and therapy of some malignancies in humans, such as promyelocytic leukaemia, notably in combination chemotherapy. Unfortunately, lack of response, recurrence, toxicity and resistance are observed. Worldwide clinical trials have been set up to evaluate the treatment of mammary carcinoma with retinoids. It appears important to determine, before starting treatment, whether oestrogen or retinyl receptors are present in the tumor tissue.

Humans↗
PubMed1996

Retinoic acid nuclear receptor alpha(RAR alpha) plays a major role in retinoid-mediated inhibition of growth in human breast carcinoma cells.

Retinoids mediate their actions via retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Each of class of these nuclear retinoid receptor is further subdivided into three species namely alpha, beta and gamma. Recently studies demonstrated that estrogen receptor (ER)-positive human breast cancer (HBC) cell lines are sensitive and ER-negative cell lines are resistant to growth inhibitory effects of retinoic acid (RA). In this study, we found that only RAR alpha mRNA levels was strongly correlated with ER-status. To further investigate the major role of RAR alpha in retinoid-mediated inhibition of growth, we transfected RAR alpha cDNA into two RA-resistant ER-negative HBC cell lines. Analysis of different clonal populations of RAR alpha transfectants from each cell line revealed growth inhibition by retinoids. Our results demonstrated that RAR alpha plays a major role in mediating retinoids inhibition of growth in HBC cells and adequate levels of RAR alpha are required for such an effect.

Breast Neoplasms↗
PubMed1996

[Abnormal central nervous conduction in long-term treatments with retinoids].

INTRODUCTION: Neurological manifestations are uncommon among the undesirable effects of systemic retinoid therapy. We observed a case of axial rigidity imputable to acitretine. Somesthesic evoked potentials were also altered. We therefore searched for such abnormal findings in patients given long-term systemic retinoid therapy. PATIENTS AND METHODS: A neurological exploration was performed in two groups of patients, G1 and G2, with psoriasis and no neurological complaint. The exploration included a physical examination, a study of the somesthesic evoked potentials of all 4 limbs and an electromyogram in case of abnormal findings. There were 8 patients (3 women, 5 men, mean age 56 years, age range 39-71) in G1 treated with systemic retinoids for a mean 140 months (80-185). Cumulative dose was 50 to 280 g with a daily dose of 0.2 to 0.6 mg/kg/day, i.e 20 to 50 mg/d of etretinate or acitretine. In G2, there were 5 subjects (mean age 42 years, range 21-52) with psoriasis (mean duration 20 years range 14-25) who had never been treated with systemic retinoids. RESULTS: Alterations in somesthesic evoked potentials were observed in 7 of the 8 patients in G1. Bilateral disturbances were seen in 6 cases, demonstrating abnormal lemniscal central nervous conduction in the dorsal and/or cervical level in 3 cases and the cervical level alone in 3 cases. There was one asymmetrical case involving the lumbar level on the right and the dorsal and/or cervical level on the right. Only one of the 5 controls in G2 had a minimal unilateral reduction in somesthesic evoked potentials involving the lower limb. Direct effect of systemic retinoids was retained in absence of any other cause due to metabolic, toxic or deficient disorders or spinal compression. CONCLUSION: Long-term use of systemic retinoids induces frequent latent neurological anomalies expressed as lemniscal central nervous conduction. It is hypothesized that pathogenesis involves changes in the lipid composition of the nervous membranes.

Adult↗
PubMedDate not supplied

Antiproliferative activity and apoptosis induced by retinoic acid receptor-gamma selectively binding retinoids in neuroblastoma.

Retinoids modulate several cell functions and especially inhibit the growth of tumor cells. Their biological activity is mediated by retinoic acid receptors (RARs), of which three subtypes (alpha, beta, gamma) have been identified. In human neuroblastoma (NB) reduced endogenous RAR-gamma expression was suggested to diminish the sensitivity for retinoids, to promote proliferation, and to contribute to the malignant phenotype. To correlate receptor selectivity with in vitro activity, we analysed the effect of six synthetic retinoids with selectivity for human RAR-alpha/beta/gamma on the human LAN-5 NB cell line and compared it with the natural compound all-trans-retinoic acid (ATRA). Apoptosis was determined by flow-cytometry using terminal-deoxynucleotidyl transferase to end-label DNA fragments in situ in apoptotic cells. The antagonist for RAR-beta/gamma CD2665 as well as the selective agonists for RAR-alpha CD336 and RAR-beta CD2019 were less effective in growth inhibition than ATRA. In contrast, the synthetic RAR-gamma selective agonists CD437 and CD2325 induced a concentration- and time-dependent antiproliferative effect, which was similar or even more pronounced than ATRA. In contrast to ATRA, the adition of CD437 and CD2325 did not induce morphological changes typical of NB cell maturation but resulted in morphological features consistent with the occurrence of programmed cell death. Flow-cytometric analysis showed that in contrast to ATRA the addition of CD 437 and CD 2325 results in progressive time-dependent increase of apoptotic cells (25.9% and 57.7% after 72 hours). In conclusion, our study demonstrates RAR-gamma selectively binding retinoids dramatically suppress NB cell growth, primarily by inducing programmed cell death rather than by cell differentiation. Since advanced or disseminated NB tumors endogenously express low levels of RAR-gamma and lack of apoptosis is involved in tumor progression, RAR-gamma selectively binding retinoids may be more appropriate retinoids for clinical trials in NB.

Apoptosis↗
PubMed1998

Regulation of RAR beta expression by RAR- and RXR-selective retinoids in human lung cancer cell lines: effect on growth inhibition and apoptosis induction.

Retinoids regulate the growth and differentiation of human tracheobronchial epithelial cells. In this study, we investigated the effects of all-trans-retinoic acid (trans-RA) and receptor class-selective retinoids on the growth and apoptosis of human lung cancer cell lines. Trans-RA significantly inhibited the growth of Calu-6 and H460 cells, accompanied by induction of RA receptor (RAR) beta expression. In contrast, it had little effect on the growth of H292, SK-MES-1 and H661 lung cancer cell lines, in which RAR beta expression was not induced. Stable expression of RAR beta in RAR beta-negative, trans-RA-resistant SK-MES-1 and H661 lung cancer cells led to recovery of trans-RA-induced growth inhibition, which occurred, however, only at low serum concentration. Using fluorescent microscopy and the terminal deoxyribonucleotidyl transferase (TdT) assay, we demonstrated that induction of apoptosis by trans-RA contributed to its growth-inhibitory effect in trans-RA-sensitive lung cancer cell lines. Analysis of RAR-selective and retinoid X receptor (RXR)-selective retionoids showed that activation of both RARs and RXRs could induce growth inhibition in trans-RA-sensitive lung cancer cells. Also, an additive synergistic effect on growth inhibition and RAR beta induction was observed when cells were treated with combinations of RAR-selective and RXR-selective retinoids. Together, our results show that expression of RAR beta plays a role in mediating retinoid response in lung cancer cells and that activation of RARs or RXRs contributes to induction of RAR beta, growth inhibition and apoptosis by retinoids.

Apoptosis↗
PubMed1996

Inhibition of rabbit collagenase (matrix metalloproteinase-1; MMP-1) transcription by retinoid receptors: evidence for binding of RARs/RXRs to the -77 AP-1 site through interactions with c-Jun.

Treatment of synovial fibroblasts with retinoic acid (RA) decreases their expression of collagenase (matrix metalloproteinase-1 or MMP-1), an enzyme that degrades interstitial collagens and contributes to the pathology of rheumatoid arthritis. This inhibition results, at least in part, from RA-induced decreases in the mRNA for the transactivators Fos and Jun (with concominant increases in RAR mRNA) and by sequestration of Fos/Jun by RARs/RXRs. Previously, we provided evidence that retinoid receptors are also present in complexes that bind to fragments of rabbit MMP-1 promoter DNA containing an AP-1 site at -77 (Pan et al., 1995, J. Cell. Biochem., 57:575-589). However, it was unclear whether RARs and retinoid X receptors (RXRs) were binding directly to the DNA or indirectly through another protein. We now use a sensitive MMP-1 promoter/luciferase reporter construct to confirm the transcriptional role of the AP-1 site at -77. In addition, with electrophoretic mobility shift analyses (EMSAs), antibody "supershifts" and DNAase 1 footprinting, we examine the interaction of retinoid receptors and AP-1 protein on the MMP-1 promoter. We demonstrate that RARs, RXRs, and c-Jun form a complex at the AP-1 site in which c-Jun binds directly to the DNA and apparently tethers the retinoid receptors to the complex. We conclude that retinoid receptors/AP-1 protein interactions at the DNA may provide an additional means of controlling collagenase gene transcription by retinoids.

Animals↗
PubMed2005

Retinoid signaling competence and RARbeta-mediated gene regulation in the developing mammalian telencephalon.

To study retinoid signaling in the developing telencephalon, we transfected a retinoid reporter gene into different regions of developing telencephalon. We found that the ventral telencephalon was more competent to retinoid signaling than the dorsal telencephalon. Moreover, among all retinoic acid receptors (RARs) and retinoid X receptors (RXRs), RARbeta was strongly induced by retinoic acid in the ventral telencephalon, suggesting that RARbeta might be involved in retinoid signaling competence. The RT-PCR analysis indicated that RARbeta was selectively expressed in the developing striatum of ventral telencephalon. We then demonstrated that null mutations of RARbeta gene resulted in reduction of striatal-enriched tyrosine phosphatase (STEP) mRNA in the striatum of RARbeta-/- mutant mice. Conversely, the gain-of-function study showed that ectopic expression of RARbeta1 in the cerebral cortex enhanced STEP expression, and the effect was RARbeta-isoform specific. Our study identified RARbeta as an important molecule for transducing retinoid signals in developing ventral telencephalon.

Animals↗
PubMed1993

Induction of RAR-beta 2 gene expression in embryos and RAR-beta 2 transactivation by the synthetic retinoid Ro 13-6307 correlates with its high teratogenic potency.

Vitamin A (retinol), its metabolite all-trans retinoic acid (RA), and many synthetic analogs (retinoids) express variable potencies as teratogens. Although biological activities of retinoids are mediated by nuclear RA receptors (RARs) and retinoid X receptors (RXRs), it is not known if any of these receptors mediate teratogenicity, and if the potency also depends on the nature of the ligand-receptor interactions. Previous evidence has implicated that one specific isoform, RAR-beta 2, does play a role in mediating retinoid teratogenicity. Here, we employed an aromatic retinoid with a triene side chain, Ro 13-6307, to study its interactions with RAR-beta 2 since its teratogenicity is much higher and its accessibility to the embryo is much lower than RA. A fully teratogenic dose of Ro 13-6307 (10 mg-kg) given to pregnant mice preferentially elevated the level of RAR-beta 2 mRNA in susceptible embryonic regions (maximal induction, 10- to 12-fold above control in limb buds) in a manner comparable to a fully teratogenic dose of all-trans RA (100 mg-kg). Using the RAR-beta 2 promoter linked to a reporter gene in cotransfection experiments, the efficacy of Ro 13-6307 and RAR-beta 2 in transcription transactivation was found to be 30-40 times greater than all-trans RA. Since the teratogenic potency of Ro 13-6307 is estimated from a previous study to be 44-fold greater than all-trans RA, we suggest that the teratogenicity of this synthetic retinoid is generally proportional to its ability to enhance receptor function.

Animals↗
PubMed1979

[Beneficial effect of oral retinoid in psoriatic hyperproliferation. Autoradiographic studies on involved and non involved skin (author's transl)].

In 16 patients with generalized psoriasis treated with oral retinoid (Ro 10-9359; 1 mg/kg body weight/(day) autoradiographic studies were performed before, and 24 h, 48 h, 1 week and 3 weeks after beginning of treatment on involved and non involved epidermis. During the first week no significant changes of all cellular parameters were found. However, after 3 weeks of continuing medication the increased 3H-thymidine labelling index was markedly lowered and the prolonged DNA synthesis time was shortened; whereas, the cell cycle time remained unaffected. The findings revealed that oral retinoid has a distinct influence on epidermal cell proliferation towards normalization in both involved and non involved epidermis in psoriasis. The time needed for this effect indicates that the drug does not directly interfere with the cell cycle. It seems reasonable, therefore, to combine oral retinoids as a basic adjuvant drug with other antipsoriatic techniques, such as retinoid + anthralin, retinoid + PUVA, retinoid + UVB.

Cell Cycle↗
PubMed1996

Retinoids modulate the effect of PTH and calcitriol on EGF receptor expression in UMR 106-01 cells.

Although osteoblast proliferation is a prominent feature of osteitis fibrosa, studies in vitro using osteoblast-like cells have shown that parathyroid hormone (PTH) impairs cell growth. Recent studies in our laboratory have shown that PTH increases epidermal growth factor (EGF) receptor expression in UMR 106-01 osteoblast-like cells, and thus, osteoblast proliferation may occur as a result of an enhanced response of the osteoblast to EGF. In the present studies we investigated the effect of calcitriol and the influence of retinoids on the regulation of EGF receptors. Calcitriol increased 125I-EGF binding 2.5-3-fold after 72 hours of incubation and was maximal at a calcitriol dose of 100 nM. Scatchard analysis showed that this effect was due to increased receptor number. In contrast, all-trans retinoic acid or 9-cis retinoic acid alone, even at 10 microM, caused less than a 50% increase in 125I-EGF binding. However, the effect of calcitriol was totally abolished in the presence of all-trans retinoic acid. 9-cis retinoic acid was equivalent with all-trans retinoic acid in this regard. In the presence of either retinoid, the stimulatory effect of PTH was totally eliminated and EGF binding was actually decreased below control values. Additional studies revealed that retinoic acid decreased PTH-stimulated cAMP generation in a dose-dependent manner. These data are consistent with our previous studies which showed that the effect of PTH on the induction of EGF receptors was mediated by a cAMP-dependent mechanism. The inhibition of the calcitriol effect by retinoids is consistent with the requirement of the retinoid-X-receptor (RXR) for binding of the vitamin D receptor (VDR) to its target sequences in DNA. These data indicate that EGF receptors in UMR 106-01 cells are up-regulated by PTH and calcitriol and that this process can be modulated by retinoids. Retinoids, therefore, may play a major role in the regulation of osteoblast function by PTH and calcitriol.

Animals↗
PubMed1996

Differentiation effect of acyclic retinoid on acute promyelocytic leukemia cells.

Acyclic retinoid (all-trans-3, 7, 11, 15-tetramethyl-2, 4, 6, 10, 14-hexadecapentaenoic acid) binds cellular retinoic acid-binding protein with an affinity similar to that of all-trans retinoic acid and induces differentiation of human hepatoma cell lines and a human acute myelogenous leukemia cell line (HL-60). We investigated the in vitro efficacy of acyclic retinoid to induce the differentiation of acute promyelocytic leukemia (APL) cells using primary cultured cells obtained from 11 APL patients. Five days' incubation with acyclic retinoid effected a dose-dependent induction of differentiation. Cells from eight patients showed maximum differentiation at 10(-6) M acyclic retinoid. Cells from one patient required 10(-5) M for maximum differentiation, while those from two patients exhibited moderate differentiation at 10(-5) M. Five days' incubation with acyclic retinoid (10(-7) approximately 10(-5) M) did not affect the viability or number of cells from any patient except one, whose cells showed a slight decrease in viability at 10(-5) M. Thus, we conclude that acyclic retinoid induced the differentiation of primary cultured APL cells at concentrations of 10(-6) approximately 10(-5) M, a range at which it is not toxic.

Antineoplastic Agents↗
PubMed1990

Retinoids enhance the number of EGF receptors in corneal endothelial cells.

Corneal endothelium appears to be an important target tissue for retinoids and epidermal growth factor (EGF). We report here that retinoic acid, or its synthetic analogue CBS-211 A (10(-8)-10(-7) M) dose-dependently enhances the mitogenic effect of EGF on cultured bovine corneal endothelial cells (BCEC). Furthermore, retinoid treatment, especially with CBS-211 A, increases the EGF-binding capacity of BCEC without any modification of EGF receptor affinity. The addition of cycloheximide (0.5 microgram ml-1) to cultures simultaneously with retinoids suppressed the retinoid effect on EGF-binding, whereas this protein synthesis inhibitor was ineffective when added 24 hr later. These results suggest that retinoids could induce the expression of EGF receptors on BCEC as an early event. This study, which demonstrates a cooperation between retinoids and EGF in corneal endothelium, could explain the beneficial effect of retinoic acid previously reported on this tissue repair in vivo. Our data could offer clues for new pharmaceutical strategies in ophthalmology therapy.

Animals↗