RNA interference targeting transforming growth factor-beta type II receptor suppresses ocular inflammation and fibrosis.
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PURPOSE: Transforming growth factor-beta(TGF-beta) is an important mediator of wound healing responses. In the eye, TGF-beta activity has been implicated in causing corneal haze after laser surgery and subconjunctival scarring following glaucoma surgery. The purpose of the study was to determine whether small interference RNAs (siRNAs) targeting the type II receptor of TGF-beta (TbetaRII) could be used to suppress the TGF-beta action. METHODS: TbetaRII specific siRNAs designed from the human gene sequence were transfected into cultured human corneal fibroblasts. The protein and transcript levels of the receptor were determined by immunofluorescence, western blotting, and real time PCR. Immunofluorescence and immunoblotting were carried out to examine fibronectin assembly. A wound closure assay was used to assess cell migration in in vitro fibroblast cultures. In addition, the in vivo effects of TbetaRII siRNA were evaluated in a mouse model of ocular inflammation and fibrosis generated by subconjunctival injection of phosphate buffered saline and latex beads. Mouse TbetaRII siRNA was introduced into experimental eyes. Cellularity on tissue sections was evaluated after staining with hematoxylin and eosin. Collagen deposition was visualized by picrosirius red staining. RESULTS: TbetaRII siRNAs abrogated the receptor transcript and protein expression in cultured corneal fibroblasts. The gene knockdown inhibited fibronectin assembly and retarded cell migration. In the mouse model, introduction of TbetaRII specific siRNA significantly reduced the inflammatory response and matrix deposition. CONCLUSIONS: TbetaRII specific siRNAs were efficacious both in vitro and in vivo in knocking down the TGF-beta action. A direct application of siRNA into eyes to downregulate TbetaRII expression may provide a novel therapy for preventing ocular inflammation and scarring. (+info)
Health-related quality of life among adolescents with allergy-like conditions - with emphasis on food hypersensitivity.
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BACKGROUND: It is known that there is an increase in the prevalence of allergy and that allergic diseases have a negative impact on individuals' health-related quality of life (HRQL). However, research in this field is mainly focused on individuals with verified allergy, i.e. leaving out those with self-reported allergy-like conditions but with no doctor-diagnosis. Furthermore, studies on food hypersensitivity and quality of life are scarce. In order to receive information about the extent to which adolescent females and males experience allergy-like conditions and the impact of these conditions on their everyday life, the present study aimed to investigate the magnitude of self-reported allergy-like conditions in adolescence and to evaluate their HRQL. Special focus was put on food hypersensitivity as a specific allergy-like condition and on gender differences. METHODS: In connection with lessons completed at the children's school, a study-specific questionnaire and the generic instrument SF-36 were distributed to 1488 adolescents, 13-21 years old (response rate 97%). RESULTS: Sixty-four per cent of the respondents reported some kind of allergy-like condition: 46% reported hypersensitivity to defined substances and 51% reported allergic diseases (i.e. asthma/wheezing, eczema/rash, rhino-conjunctivitis). A total of 19% reported food hypersensitivity. Females more often reported allergy-like conditions compared with males (p < 0.001). The adolescents with allergy-like conditions reported significantly lower HRQL (p < 0.001) in seven of the eight SF-36 health scales compared with adolescents without such conditions, regardless of whether the condition had been doctor-diagnosed or not. Most adolescents suffered from complex allergy-like conditions. CONCLUSIONS: The results indicate a need to consider the psychosocial impact of allergy-like conditions during school age. Further research is needed to elucidate the gender differences in this area. A team approach addressing better understanding of how allergy-like conditions impair the HRQL may improve the management of the adolescent's health problems, both in health-care services and in schools. (+info)
Spontaneous ocular surface inflammation and goblet cell disappearance in I kappa B zeta gene-disrupted mice.
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PURPOSE: The ocular surface epithelium is part of the mucosal defense system. Because transcription factor NF-kappa B in mucosal epithelial cells plays a central role in regulating the genes that govern the onset of mucosal inflammatory responses, we examined the role of a regulator of NF-kappa B, I kappa B zeta, in murine ocular surface inflammation. METHODS: The eyes of I kappa B zeta(-/-) mice were analyzed biomicroscopically and histologically. I kappa B zeta expression in normal mouse cornea and conjunctiva was examined by RT-PCR. The results were compared with those obtained in other tissues by real-time PCR. I kappa B zeta mRNA on the ocular surface and in other mucosal tissues was localized by in situ hybridization. RESULTS: I kappa B zeta(-/-) mice manifested chronic inflammation, specifically in the ocular surface, but not in other tissues. In normal mice, I kappa B zeta was expressed in a variety of mucosal tissues. The I kappa B zeta transcript was predominantly distributed in the epithelia of these tissues. As inflammatory symptoms progressed on the ocular surface of I kappa B zeta(-/-) mice, inflammatory cells, mainly CD45R/B220(+) and CD4(+) cells, intensely infiltrated the submucosa of the conjunctival epithelia. This infiltration was accompanied by an almost complete loss of goblet cells in the conjunctival epithelia. CONCLUSIONS: The authors postulate that I kappa B zeta in the ocular surface epithelia negatively regulates the pathologic progression of ocular surface inflammation. (+info)
Direct action of platelet activating factor (PAF) induces eosinophil accumulation and enhances expression of PAF receptors in conjunctivitis.
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PURPOSE: The goal of the present study was to investigate the role of platelet activating factor (PAF) and PAF receptor (PAF-R) in the recruitment of eosinophils into the conjunctiva in the course of PAF induced conjunctivitis. Eosinophils are important players in the immediate hypersensitivity reactions and in allergic conjunctivitis. PAF-R is expressed in many ocular tissues including conjunctival cells. Although it is known that PAF is one of the most potent chemotactic agents for the recruitment of eosinophils, factors responsible for it in conjunctivitis are not clear. Colocalization analysis has been employed to quantify the degree of colocalization of major basic protein (MBP) and PAF-R antigens in the course of PAF induced conjunctivitis. METHODS: A 1% solution of PAF was applied in eye drops to male Brown Norway rats. Eyes were harvested with intact conjunctivas at different time points and examined using histology, immunohistochemistry, confocal immunofluorescence microscopy, and reverse transcription-polymerase chain reaction. PAF-R and MBP (a marker of eosinophils) antibodies have been used for immunohistochemical studies. Quantitative analysis of the colocalization of PAF-R and major basic protein (MBP) antigens was performed. RESULTS: Instillation of PAF caused a time dependent recruitment of eosinophils. Eosinophils revealed PAF-R in the intact state. An influx of eosinophils into the conjunctiva was caused by the interaction of PAF with PAF-R and, possibly, with MBP antigen. PAF appeared to enhance the expression of PAF-R by eosinophils and to act toward the PAF-R directly, without chemokine mediation. CONCLUSIONS: Quantitative colocalization analysis helped to determine that the recruitment of eosinophils in PAF induced conjunctivitis is accomplished via direct action of PAF toward the PAF-R. It also ensured an objective evaluation of the changes of the degree of colocalization of MBP and PAF-R antigens and the degree of PAF-R expression in dynamics, the findings not otherwise obtainable using qualitative approaches alone. (+info)
Clustered outbreak of skin and eye complaints among catering staff.
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In August 2002, kitchen staff at a hotel in Central Scotland experienced skin and eye problems believed to be related to their working environment. Of a total of 20 staff, eight cooks reported problems with a painful red skin affecting the face, eyelids, side and front of neck as well as burning, gritty eyes. Five of the affected individuals were clinically assessed in April 2003. The overall clinical impression was of conjunctivitis and sunburn-like erythema. Examination of the data sheets of all cleaning agents and sprays used within the kitchen pointed against an environmental phototoxin. The kitchen area was inspected and two electric fly killers positioned on the ceiling and sidewalls were found to be incorrectly fitted with UVC tubes. The output of these tubes was spectroradiometrically assessed. The recommended unprotected skin and eye exposure limit was reached in 14 s at a distance of 30 cm from the tubes. An exposure of about 60 s would be sufficient to induce minimal erythema in someone of skin type I/II. These results demonstrate the importance of exposure to ultraviolet radiation as a possible cause of facial erythema and conjunctivitis, no matter how unlikely this may seem. It is recommended that there should be increased awareness of the need to fit the correct type of lamps to electric fly killers and other devices that incorporate UV lamps. (+info)
Lesions caused by ricin applied to rabbit eyes.
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PURPOSE: Ricin, a highly potent toxin from castor beans, is a potential biological weapon that could be dispersed in the air as dust or aerosol. In these forms, ricin, besides being inhaled, could reach unprotected eyes. The present research was performed to ascertain the lesions that the toxin causes when applied to rabbit eyes. METHODS: Ricin was applied to rabbit eyes in solution, in quantities ranging from 1 to 100 mug. Animals were observed until death, when eyes and internal organs were removed and fixed. Sections were stained and examined microscopically. RESULTS: Ricin caused inflammation of the eyes and adnexa, visible both macroscopically and histologically. The damage was greatly reduced by rinsing the eyes with 10% lactose, provided the rinsing was done almost immediately after application of the toxin. Rinsing with phosphate-buffered saline (PBS) had no effect. With the highest dosage, congestion of internal organs was also apparent. CONCLUSIONS: Application of ricin to eyes causes local damage, mainly of the inflammatory type. The ineffectiveness of rapid rinsing with PBS and the partial efficacy of rapid rinsing with lactose indicate that the toxin quickly binds to and is taken up by cells. The lesions of internal organs show that ricin applied to the eyes can be absorbed, pass into the circulation, and, at least at some dosages, damage internal organs. (+info)
Long term outcome of trichiasis surgery in the Gambia.
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BACKGROUND: Trichiasis surgery is believed to reduce the risk of losing vision from trachoma. There are limited data on the long term outcome of surgery and its effect on vision and corneal opacification. Similarly, the determinants of failure are not well understood. METHODS: A cohort of people in the Gambia who had undergone surgery for trachomatous trichiasis 3-4 years earlier was re-assessed. They were examined clinically and the conjunctiva was sampled for Chlamydia trachomatis polymerase chain reaction (PCR) and general bacterial culture. RESULTS: In total, 141/162 people were re-examined. Recurrent trichiasis was found in 89/214 (41.6%) operated eyes and 52 (24.3%) eyes had five or more lashes touching the globe. Corneal opacification improved in 36 of 78 previously affected eyes. There was a general deterioration in visual acuity between surgery and follow up, which was greater if new corneal opacification developed or trichiasis returned. Recurrent trichiasis was associated with severe conjunctival inflammation and bacterial infection. C trachomatis was detected in only one individual. CONCLUSIONS: Recurrent trichiasis following surgery is a common potentially sight threatening problem. Some improvement in the cornea can occur following surgery and the rate of visual loss tended to be less in those without recurrent trichiasis. The role of conjunctival inflammation and bacterial infection needs to be investigated further. Follow up of patients is advised to identify individuals needing additional surgical treatment. (+info)
Ocular leishmaniasis: a case report.
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Cutaneous leishmaniasis (CL) is a protozoal disease which is endemic in Iran usually caused by Leishmaniasis major and Leishmaniasis tropica and transmitted by the bite of a sandfly. In Isfahan province CL is highly prevalent and we observe some unusual clinical features of disease. The eyelid is rarely involved possibly because the movement of the lids prevents the fly vector from biting the skin in this region. We report a case of ocular leishmaniasis with eyelid and conjunctival involvement that had simulated chalazion and was complicated with trichiasis. The patient was diagnosed by direct smear, culture, and PCR from the lesions. He was treated with systemic sodium stibogluconate (20 mg/kg/day) for 20 days and subsequently surgery for trichiasis. The patient was clinically cured with this treatment, however the disease had left complications, including palpebral and conjanctival scaring, corneal opacity, and eyelash loss. (+info)