Single Ultraviolet Exposure Research Articles

Eradication of skin microbiota restores cytokine production and release in polymorphic light eruption.

Polymorphic light eruption (PLE) has been mechanistically linked to cytokine abnormalities. Emerging preclinical evidence posits the skin microbiome as a critical modulator of ultraviolet (UV)-induced cytokine expression, thereby influencing subsequent immune responses. This intricate relationship remains underexplored in the context of PLE. Hence, we investigated the differential responses between disinfected and non-disinfected skin following both single and repetitive exposures to solar-simulated UV radiation in patients with PLE. An experimental, half-body pilot study was conducted involving six PLE patients and 15 healthy controls. Participants' skin was exposed to single and multiple doses of solar-simulated UV radiation, both in disinfected and in non-disinfected skin areas. The co-primary outcomes were PLE score and cytokine expression in blister fluid analysed through OLINK proteomic profiling. Secondary outcomes were erythema, pigmentation, induction of apoptotic cells in vacuum-generated suction blisters, and density of infiltrate in skin biopsies of PLE patients. Among the 71 cytokines analysed, baseline expression levels of 20 specific cytokines-integral to processes such as apoptosis, inflammation, immune cell recruitment, cellular growth, and differentiation-were significantly impaired in PLE patients compared with healthy controls. Notably, skin disinfection reversed the observed cytokine imbalances following a single UV exposure at the minimal erythema dose (MED) level and exhibited even more pronounced effects after multiple UV exposures. However, no significant differences were evident in PLE score, erythema, pigmentation, or rates of apoptotic cell induction upon UV radiation. These findings provide evidence for UV-driven cytokine regulation by the skin microbiota and imply microbiome involvement in the PLE immune response.

Nerve Growth Factor (NGF) as Partaker in the Modulation of UV-Response in Cultured Human Conjunctival Fibroblasts.

Corroborating data sustain the pleiotropic effect of nerve growth factor (NGF) in the protection of the visual system from dangerous stimuli, including ultraviolet (UV). Since UV exposure might promote ocular surface changes (conjunctival inflammation and matrix rearrangement), as previously reported from in vivo studies sustaining some protective NGF effects, in vitro cultures of human conjunctival fibroblasts (FBs) were developed and exposed to a single UV exposure over 15 min (0.277 W/m2), either alone or supplemented with NGF (1–10–100 ng/mL). Conditioned media and cell monolayers were collected and analyzed for protein release (ELISA, ELLA microfluidic) and transcript expression (real-time PCR). A specific “inflammatory to remodeling” pattern (IL8, VEGF, IL33, OPN, and CYR61) as well as a few epigenetic transcripts (known as modulator of cell differentiation and matrix-remodeling (DNMT3a, HDAC1, NRF2 and KEAP1)) were investigated in parallel. UV-exposed FBs (i), showed no proliferation or significant cytoskeleton rearrangement; (ii), displayed a trkANGFR/p75NTR phenotype; and (iii), synthesized/released IL8, VEGF-A, IL33, OPN, and CYR61, as compared to unexposed ones. NGF addition counteracted IL8, IL33, OPN, and CYR61 protein release merely at lower NGF concentrations but not VEGF. NGF supplementation did not affect DNMT3a or HDAC1 transcripts, while it significantly upregulated NRF2 at lowest NGF doses and did not change KEAP1 expression. Taken together, a single UV exposure activated conjunctival FBs to release pro-inflammatory/fibrogenic factors in association with epigenetic changes. The effects were selectively counteracted by NGF supplementation in a dose-dependent fashion, most probably accountable to the trkANGFR/p75NTR phenotype. Further in vitro studies are underway to better understand this additional NGF pleiotropic effect. Since UV-shield impairments represent a worldwide alert and UV radiation can slowly affect ocular surface homeostasis (photo-ageing, cataract) or might exacerbate ocular diseases with a preexisting fibrosis (pterygium, VKC), these findings on NGF modulation of UV-exposed FBs might provide additional information for protecting the ocular surface (homeostasis) from low-grade long-lasting UV insults.

Erythema and Acclimatization Following Repeated Sun Exposure: A Modeling Study

The development of a computational model is described that allows time-varying erythema and acclimatization to be determined following repeated exposure to solar ultraviolet (UV) radiation. Good agreement was observed between experimental data and model predictions. Results are presented that illustrate how daily, adventitious sun exposure over the course of a year can result in occasional erythema generally in the late spring/early summer, while at the same time showing how the photoadaptive response of the skin changes throughout the year at different latitudes and for different sun-reactive skin types. The model is predicated on three physiological responses; the erythemal response as a function of increasing UV dose, the time courses of erythema and adaptation in response to a single UV exposure. Mathematical models complement observational data and the outputs from the model may help in planning future experimental studies, as well as providing insights into mechanistic responses.

Optimization of Single-Step UV Exposure for Fabrication of Integrated Optical Device by Imprinting

In this paper, a single ultra-violet exposure for multi-height structure was used to fabricate an optical-fiberintegrated planar lightwave circuit (PLC) splitter using a thermal imprinting technique. The 1 × 8 tapered multimode PLC splitter was designed with a trench at a depth of 50 μm and a variable width ranging from 50 μm to 690 μm for the insertion of waveguide and fiber structures measuring 125 μm × 87.5 μm in order to minimize insertion loss. Photolithography with a Cr layer and bottom anti-reflection coating (BARC) was utilized to fabricate a multi-height photoresist structure, and the effect of the thick Cr layer and BARC on the geometry was investigated. Scanning electron microscopy of the fabricated structures showed that a Cr thickness of 50 nm and BARC provided the ideal geometry with a minimal undercut and sidewall roughness. Based on the characterization of the imprinted splitter, the average value and uniformity of optical loss between the channels were 10 dB and less than 0.42 dB, respectively.

Automation Highlights from the Literature

Automation Highlights from the Literature

Hydrogels Based on Dual Curable Chitosan-graft-Polyethylene Glycol-graft-Methacrylate: Application to Layer-by-Layer Cell Encapsulation

Ultraviolet (UV) photo-cross-linkable hydrogels have been commonly used for three-dimensional (3D) encapsulation of cells. Previous UV cross-linkable hydrogels have employed one-shot hardening of mixtures of hydrogels and cells. Here we propose an alternative method of making hydrogel-encapsulated cell constructs through layer by layer (LBL) buildup of alternating layers of cells and hydrogel. The LBL method potentially permits better spatial control of different cell types and control of cell orientation. Each hydrogel layer must be hardened before deposition of the next layer of cells. A UV-curable gel precursor that can also be gelled at physiological temperature is desirable to avoid repeated UV exposure of cells after deposition of each successive hydrogel layer. We designed, synthesized, and applied such a precursor, dual-curable-both thermoresponsive and UV-curable-chitosan-graft-polyethylene glycol-graft-methacrylate (CEGx-MA) copolymer (x is the PEG molecular weight in Daltons). We found that CEG350-MA copolymer solutions (5 wt % polymer) formed physical gels at approximately 37 degrees C and could be further photopolymerized to form thermally stable dual-cured hydrogels. This material was applied to the creation of a two-layer LBL smooth muscle cell (SMC)/hydrogel construct using temperature elevation to approximately 37 degrees C to gel each hydrogel layer. The physically gelled two-layered hydrogel/cell construct was finally exposed to a single UV shot to improve its mechanical properties and render it thermally stable. CEG350-MA solution and gel are nontoxic to SMCs. Cells remained mostly viable when they were encapsulated inside both physically gelled and dual-cured CEG350-MA and suffered little damage from the single brief UV exposure. The combination of LBL tissue engineering with a dual curable hydrogel precursor such as CEG350-MA permits the buildup of viable thick and complex tissues in a stable, biocompatible, and biodegradable matrix.

An Anchor-Board-Based Flexible Optoelectronic Harness for Off-Chip Optical Interconnects

A flexible optical interconnect prototype at board/card-level using a novel anchor-board-based optoelectronic (OE) harness is experimentally demonstrated at 2 Gb/s. The flexible OE harness comprises a thin polyimide film laminated on two narrow anchor boards where edge-emitting lasers (EELs) and p-i-n photodetectors (PDs) are positioned and integrated with polymer waveguides. High-speed electronics are surface-mounted on two separate printed-circuit boards, making the OE harness detachable and field-reparable. A large EEL-PD lateral alignment tolerance of >1.5 mm for a 15-cm interconnect distance is achieved without any microlens. One or multiple channels can be simultaneously aligned and formed during one single ultraviolet exposure. A cost-effective field repair strategy is thus envisioned.

Grayscale lithography by a polymer photomask doped with laser dye

This article reports on the development of a novel grayscale photomask which operates on the basis of differential absorption of ultraviolet (UV) light in photoabsorbing material. The developed photomask is made of a patterned, moldable polymer (polydimethylsiloxane) doped with a laser dye (Coumarin 314). The doped polymer functions as photoabsorbing material. Due to the moldable nature of polydimethylsiloxane, micro- and nanostructures can be created on its surface from a complementary mold relief. By adjusting the thickness of patterns formed on the photomask, concentration of the dye in the polymer, and UV exposure dose, a multitude of unique multidimensional microstructures can be fabricated with desired geometries and dimensions. Using the developed polymer photomask with a standard UV source, three-dimensional microstructures with different heights have been formed in positive photoresist by a single UV exposure step. This method is inexpensive compared to other grayscale lithography techniques and relatively easy to implement due to its process simplicity.

Change of biophysical properties of the skin caused by ultraviolet radiation‐induced photodamage in Koreans

Ultraviolet (UV) irradiation affects the function and complexion of the skin by inducing changes in physical properties through formation of erythema, proliferation of epithelial cells, DNA damage, activation or inactivation of various enzymes and proteins, and free radical formation. In this study, the authors intended to observe the overall course of changes in barrier function and reflectance of the skin induced by photodamage, and healing reaction in the course of time, and alteration of the skin complexion. The subjects were chosen from 15 healthy Korean men 20-35 in age, that fall into the category of Fitzpatrick's skin types II, III, and IV without history of recent exposure to sunlight, photosensitivity, or having taken any drugs that induce phototoxicity or photoallergic reactions. The subjects were artificially exposed to suberythemogenic dose [0.5 minimal erythemal dose (MED), 0.75 MED], 1 MED and high dose (2.5 MED) by solar simulator, and changes in skin barrier function and skin reflectance were assessed with a Tewameter, a Corneometer, and a Colorimeter for 4 weeks. Transepidermal water loss (TEWL) increased abruptly at Day 1 of single solar UV (SSUV) exposure, and slowly returned to the original level from Day 2/Day 3. In the case of exposure with 0.75 MED, it returned to the original level at Day 4 of exposure, and at Days 7 and 28 in the cases of 1 MED and 2.5 MED exposure, respectively. Water-holding capacity sharply declined at Day 1 of exposure, hitting the lowest point at Day 2, and then slowly recovered starting on Day 3. In the case of exposure with 0.75 MED and 1 MED, it returned to the original level at Days 7 and 28 in the case of 2.5 MED exposure. The a(*) values abruptly increased and reached the peak at Day 1 and slowly returned to the original level at Day 2, while the b(*) values slowly increased at Day 3, peaking at Day 7 and slowly returning to the original level thereafter. The L(*) values abruptly declined at Day 1, maintaining plateau through Day 7 and slowly returning to the baseline level thereafter. The individual typology angle (ITA degrees ) were compatible with L(*) values change. The erythema index increased abruptly at Day 1 of SSUV exposure, peaking at Day 2 and slowly returned to the original level starting at Day 3. Melanin index slowly started to increase on Day 3 of SSUV exposure, peaking at Day 7 and gradually returned to the original level thereafter. However, L(*), a(*), b(*), erythema index, and melanin index did not return to the original level during the 28-day course of this study. This study shows that in the skin of Korean subjects, changes in skin barrier function and delayed melanization do occur even in exposure to a suberythemogenic dose of SSUV. Also, given the fact that restoration of barrier function occurs as the process of melanization begins, melanization is considered to be a useful predictive indicator of the restoration of the skin barrier function after sunburn.

Novel Aspects of Intrinsic and Extrinsic Aging of Human Skin: Beneficial Effects of Soy Extract¶

ABSTRACTBiochemical and structural changes of dermal connective tissue substantially contribute to the phenotype of aging skin. To study connective tissue metabolism with respect to ultraviolet (UV) exposure, we performed an in vitro (human dermal fibroblasts) and an in vivo complementary DNA array study in combination with protein analysis in young and old volunteers. Several genes of the collagen metabolism such as Collagen I, III and VI as well as heat shock protein 47 and matrix metalloproteinase‐1 are expressed differentially, indicating UV‐mediated effects on collagen expression, processing and degradation. In particular, Collagen I is time and age dependently reduced after a single UV exposure in human skin in vivo. Moreover, older subjects display a lower baseline level and a shorter UV‐mediated increase in hyaluronan (HA) levels. To counteract these age‐dependent changes, cultured fibroblasts were treated with a specific soy extract. This treatment resulted in increased collagen and HA synthesis. In a placebo‐controlled in vivo study, topical application of an isoflavone‐containing emulsion significantly enhanced the number of dermal papillae per area after 2 weeks. Because the flattening of the dermal‐epidermal junction is the most reproducible structural change in aged skin, this soy extract appears to rejuvenate the structure of mature skin.

Novel Aspects of Intrinsic and Extrinsic Aging of Human Skin: Beneficial Effects of Soy Extract¶

Biochemical and structural changes of the dermal connective tissue substantially contribute to the phenotype of aging skin. To study connective tissue metabolism with respect to ultraviolet (UV) exposure, we performed an in vitro (human dermal fibroblasts) and an in vivo complementary DNA array study in combination with protein analysis in young and old volunteers. Several genes of the collagen metabolism such as Collagen I, III and VI as well as heat shock protein 47 and matrix metalloproteinase-1 are expressed differentially, indicating UV-mediated effects on collagen expression, processing and degradation. In particular, Collagen I is time and age dependently reduced after a single UV exposure in human skin in vivo. Moreover, older subjects display a lower baseline level and a shorter UV-mediated increase in hyaluronan (HA) levels. To counteract these age-dependent changes, cultured fibroblasts were treated with a specific soy extract. This treatment resulted in increased collagen and HA synthesis. In a placebo-controlled in vivo study, topical application of an isoflavone-containing emulsion significantly enhanced the number of dermal papillae per area after 2 weeks. Because the flattening of the dermal-epidermal junction is the most reproducible structural change in aged skin, this soy extract appears to rejuvenate the structure of mature skin.

Minimal erythema dose after multiple UV exposures depends on pre‐exposure skin pigmentation

Phototherapy consists of multiple ultraviolet (UV) exposures. Most previous studies have focused on erythema following a single UV exposure in fair-skinned persons. Although it is well known that phototherapy lowers the daily UV-threshold dose for erythema in clinical practice, this is insufficiently documented under controlled experimental conditions. The purpose of this study was to quantify the change in the daily threshold for a dose specific erythema grade after 1-4 consecutive daily UV exposures. Forty-nine healthy volunteers (skin type II-V) with varying pigmentation quantified by skin reflectance. Two UV sources were used: a narrowband UVB (Philips TL01) and a Solar Simulator (Solar Light Co.). Just perceptible erythema after 24 h was chosen as the minimal erythema dose (+); besides + and ++ were assessed. We found a positive and significant exponential relationship between skin pigmentation and UV dose to elicit a specific erythema grade on the back after 1-4 UV exposures. After repetitive UV exposures the UV dose had to be lowered more in dark-skinned persons compared with fair-skinned persons to elicit a certain erythema grade. This applied to both UV sources and all erythema grades. In the dark-skinned persons the daily UV dose after the 4 days UV exposure should be lowered by 40-50% to avoid burns compared with the single UV exposure. For the most fair-skinned persons essentially no reduction in the daily UV dose was needed. Our results indicate that the pre-exposure pigmentation level can guide the UV dosage in phototherapy.

Novel Aspects of Intrinsic and Extrinsic Aging of Human Skin: Beneficial Effects of Soy Extract

Biochemical and structural changes of the dermal connective tissue substantially contribute to the phenotype of aging skin. To study connective tissue metabolism with respect to ultraviolet (UV) exposure, we performed an in vitro (human dermal fibroblasts) and an in vivo complementary DNA array study in combination with protein analysis in young and old volunteers. Several genes of the collagen metabolism such as Collagen I, III and VI as well as heat shock protein 47 and matrix metalloproteinase-1 are expressed differentially, indicating UV-mediated effects on collagen expression, processing and degradation. In particular, Collagen I is time and age dependently reduced after a single UV exposure in human skin in vivo. Moreover, older subjects display a lower baseline level and a shorter UV-mediated increase in hyaluronan (HA) levels. To counteract these age-dependent changes, cultured fibroblasts were treated with a specific soy extract. This treatment resulted in increased collagen and HA synthesis. In a placebo-controlled in vivo study, topical application of an isoflavone-containing emulsion significantly enhanced the number of dermal papillae per area after 2 weeks. Because the flattening of the dermal-epidermal junction is the most reproducible structural change in aged skin, this soy extract appears to rejuvenate the structure of mature skin.

Possible involvement of gelatinases in basement membrane damage and wrinkle formation in chronically ultraviolet B-exposed hairless mouse.

A number of studies indicate that matrix metalloproteinase might be involved in photoaging, but little is known about their direct contribution to ultraviolet-induced histologic and morphologic changes in the skin in vivo. This study reports the relationship between changes of matrix metalloproteinase activities and ultraviolet B-induced skin changes in hairless mouse. The role of matrix metalloproteinase in the skin changes was studied by topical application of a specific matrix metalloproteinase inhibitor. The backs of mice were exposed to ultraviolet B three times a week for 10 wk. Histologic studies showed that the basement membrane structure was damaged, with epidermal hyperplasia, in the first 2 wk of ultraviolet B irradiation, followed by the appearance of wrinkles, which gradually extended in the latter half of the ultraviolet B irradiation period. We observed enhancement of type IV collagen degradation activity, but not collagenase or matrix metalloproteinase-3 activity, in extracts of ultraviolet B-irradiated, wrinkle-bearing skin. Gelatin zymographic analysis revealed that gelatinases, matrix metalloproteinase-9 and matrix metalloproteinase-2, were significantly increased in the extract. In situ zymographic study clarified that the activity was specifically localized in whole epidermis of ultraviolet B-irradiated, wrinkled skin in comparison with normal skin. The activity was induced around the basal layer of the epidermis by a single ultraviolet exposure of at least one minimal erythema dose. Furthermore, topical application of a specific matrix metalloproteinase inhibitor, CGS27023A, inhibited ultraviolet B-induced gelatinase activity in the epidermis, and its repeated application prevented ultraviolet B-induced damage to the basement membrane, as well as epidermal hyperplasia and dermal collagen degradation. Ultraviolet B-induced wrinkles were also prevented by administration of the inhibitor. These results, taken together, suggest that ultraviolet B-induced enhancement of gelatinase activity in the skin contributes to wrinkle formation through the destruction of basement membrane structure and dermal collagen in chronically ultraviolet B-exposed hairless mouse, and thus topical application of matrix metalloproteinase inhibitors may be an effective way to prevent ultraviolet B-induced wrinkle formation.

Solar-Simulated Skin Adaptation and its Effect on Subsequent UV-Induced Epidermal DNA Damage

Repeated skin exposure to ultraviolet radiation leads to increased tolerance for erythema. Whether this tolerance is accompanied by a significant protection against epidermal DNA injury has never been thoroughly investigated. In a first set of experiments we irradiated 25 healthy volunteers three times a week for 3 wk using solar-simulating tanning lamps. In addition, all individuals were exposed to a (challenge) dose of three times the initial minimal erythema dose on a small area of skin before the first and after the final exposure. On both occasions, cyclobutane pyrimidine dimers were quantified in biopsies. As expected, repeated ultraviolet exposures resulted in increased epidermal pigmentation and thickness. The ultraviolet sensitivity for erythema decreased on average by 75%. The cyclobutane pyrimidine dimer formation was reduced on average by 60%. In a second set of experiments, with a group of 13 subjects, DNA repair kinetics were assessed. Within a period of 5 d after a single, slightly erythemal dose (1.2 minimal erythema dose), levels of cyclobutane pyrimidine dimer and p53-expressing cells were determined in skin biopsies. Both markers of DNA damage were elevated upon the single ultraviolet exposure and returned to background levels after 3-4 d. This information is important when trying to minimize the risk of DNA damage accumulation after repeated exposures during a tanning course.

C-Jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid.

The aged appearance of skin following repeated exposure to solar ultraviolet (UV) irradiation stems largely from damage to cutaneous connective tissue, which is composed primarily of type I and type III collagens. We report here that a single exposure to UV irradiation causes significant loss of procollagen synthesis in human skin. Expression of type I and type III procollagens is substantially reduced within 24 hours after a single UV exposure, even at UV doses that cause only minimal skin reddening. Daily UV exposures over 4 days result in sustained reductions of both type I and type III procollagen protein levels for at least 24 hours after the final UV exposure. UV inhibition of type I procollagen synthesis is mediated in part by c-Jun, which is induced by UV irradiation and interferes with procollagen transcription. Pretreatment of human skin in vivo with all-trans retinoic acid inhibits UV induction of c-Jun and protects skin against loss of procollagen synthesis. We have reported previously that UV irradiation induces matrix-degrading metalloproteinases in human skin and that pretreatment of skin with all-trans retinoic acid inhibits this induction. UV irradiation, therefore, damages human skin connective tissue by simultaneously inhibiting procollagen synthesis and stimulating collagen breakdown. All-trans retinoic acid protects against both of these deleterious effects and may thereby retard premature skin aging.

Single exposure phototesting utilizing a divergent ultraviolet beam

Background/aims: Confident diagnosis of photosensitivity in patients with light dermatoses requires skin exposure to well determined ultraviolet (UV) light doses, most often from a solar simulator. The traditional test procedure results in a rough classification of skin sensitivity based on the minimal erythema dose (MED) found for each patient. The limited number of constant irradiance doses used during phototesting decreases the precision of the MED value. In the present study we aimed at developing the technical system for the determination of MED by using a single, centrifugally attenuating, UVB provocation.Methods: A divergent UV beam was achieved with the help of an optic lens. To investigate the irradiance profile, an irradiance acquisition system was built that produced three‐dimensional intensity maps. In addition, a laser Doppler perfusion imaging (LDPI) system was introduced in the evaluation of the skin response along with visual readings of the same exposed areas, in order to add a quantitative aspect to the assessment of erythema. The procedure was used on one test subject.Results: The divergent UV beam showed the desired profile. With the current setup 20 different UV‐dose levels could be discriminated. Relevant UV‐dose levels were determined and tested on a subject, which in practice gave results in the form of visual assessment as well as LDPI‐images. The visual or LDPI diameter gave the MED. Within the skin reaction, irradiance and the laser Doppler values could be compared mm for mm.Conclusions: A more accurate MED determination with a single UV exposure seems to be feasible by using the proposed method. Though further investigation is required, the technique appears to offer new possibilities for the association of dose to response. In addition LDPI is possibly a useful complement to the visual readings of the skin responses, since the method gives a quantification of the grade of erythema, as opposed to visual (+, ++, +++) readings that are subjective and at best semiquantitative.

Increase in neuronal Jun immunoreactivity and epidermal NGF levels following UV exposure of rat skin.

Effects of cutaneous ultraviolet (UV) irradiation on superficial nerve fibres are controversial. In the present study we demonstrate by electron microscopy that single high-dose UV exposure of rat skin results in membrane damage in peripheral nerves. Furthermore, a UV-induced accumulation of nerve growth factor (NGF) within the irradiated epidermis and a delayed increase in nuclear Jun immunoreactivity in dorsal root ganglion neurones were detected by immunohistochemistry. Our results suggest that UV-mediated alterations of axonal membranes leads to an activation of Jun transcription factor within affected neurones despite an increase in neurotrophic NGF within their innervation area.

Ultraviolet Irradiation Induces Acute Changes in Melanocytic Nevi

Ultraviolet (UV) light represents one of the factors that might play a role in the initiation and promotion of malignant transformation of human melanocytes. To determine the short-term effects of UV irradiation on melanocytic nevi in vivo, we investigated one half of symmetric melanocytic nevi after a single UV exposure with double the patient's minimal erythema dose. This half was compared with the nonirradiated, shielded half of the same nevus. The different parts were examined histologically for differences and immunohistochemically for the presence of HMB-45 antigen and proliferating cell nuclear antigen. The features were assessed quantitatively by image analysis. One week after the single UV irradiation, we observed a significant increase of suprabasally located melanocytes and a markedly enhanced expression of HMB-45, whereas proliferative activity of the cells was unchanged. In nevi that were excised 2 or 3 weeks after irradiation, no significant differences were observed between the irradiated and the nonirradiated part. The results indicate that a single UV irradiation may induce transient melanocytic activation with morphologic and histologic changes. Although these data do not formally assess resemblance to melanoma, these changes may be similar to those of melanoma in situ.

Expression of c-Fos and c-Jun in the cornea, lens, and retina after ultraviolet irradiation of the rat eye and effects of topical antisense oligodeoxynucleotides.

Immunohistochemical techniques were used to investigate c-Fos and c-Jun proto-oncogene expression in the cornea, lens, and retina after ultraviolet irradiation of the rat eye. Eyes of anaesthetised rats were exposed to 1.5 J/cm2 of ultraviolet radiation (280-380 nm). Animals were perfused 1, 6, or 24 hours after irradiation and tissue sections were incubated with specific antiserum to c-Fos and c-Jun, respectively. Non-irradiated contralateral eyes displayed no c-Fos and c-Jun immunoreactivity. One and 6 hours after ultraviolet exposure numerous c-Fos and c-Jun immunopositive nuclei were observed mainly in the epithelial cell layers of the cornea and the lens epithelium. Scattered labelled nuclei were detectable in the retinal ganglion cell layer and the inner nuclear layer. Twenty four hours after irradiation c-Fos and c-Jun protein expression returned to near control levels. Histological signs of ultraviolet damage (for example, chromatin condensation, nuclear fragmentation) were first recognisable in the corneal epithelium 6 hours after irradiation and became more apparent at later times. Thus, the rapid and sustained activation of c-Fos and c-Jun expression in the eye after single ultraviolet exposure may represent the molecular mechanism underlying ultraviolet induced photodamage and initiation of cell death. Furthermore, topical application of a c-fos antisense oligodeoxynucleotide to the ultraviolet exposed rat eye inhibited the increase in c-Fos expression in the cornea, suggesting therapeutic activity of antisense drugs in corneal malignant and infectious diseases.