UV-induced retinal proteome changes in the rat model of age-related macular degeneration.

Age-related macular degeneration (AMD) is characterized by irreversible damage of photoreceptors in the central posterior part of the retina, called the macula and is the most common cause of vision loss in those aged over 50. A growing body of evidence shows that cumulative long-term exposure to UV radiation may be harmful to the retina and possibly leads to AMD irrespective of age. In spite of many research efforts, cellular and molecular mechanisms leading to UV-induced retinal damage and possibly retinal diseases such as AMD are not completely understood. In the present study we explored damage mechanisms accounting for UV-induced retinal phototoxicity in the rats exposed to UVA and UVB irradiation using a proteomics approach. Our study showed that UV irradiation induces profound changes in the retinal proteomes of the rats associated with the disruption of energy homeostasis, oxidative stress, DNA damage response and structural and functional impairments of the interphotoreceptor matrix components and their cell surface receptors such as galectins. Two small leucine-rich proteoglycans, biglycan and lumican, were identified as phototoxicity biomarkers associated with UV-induced disruption of interphotoreceptor matrix (IPM). In addition, UVB induced activation of Src kinase, which could account for cytoskeletal rearrangements in the retina was observed at the proteomics level. Pharmacological intervention either to target Src kinase with the aim of preventing cytoskeletal rearrangements in the retinal pigment epithelium (RPE) and neuronal retina or to help rebuild damaged IPM may provide fresh avenues of treatment for patients suffering from AMD.

Sun exposure and visual field damage among children on the Adriatic Island Rab--possible initial risk factor in development of age-related macular degeneration.

The Adriatic Island Rab, situated in the northern part of the Croatian sea, is more strongly exposed to sunlight (especially from May to October) than the other parts of Croatia and most of the European countries. As consequences of higher solar radiation, significant percentage of Pseudoexfoliation of lens capsula occurs in 15% and fundus picture of AMD (Age-Related Macular Degeneration) in 18% of agriculturalists and fishermen (45-70 years old). We previously presented the first clinical study showing that in AMD the peripheral visual field is also damaged. In this clinical study we examined 68 children (8-15 years old), including following procedures: vision correction, slit lamp examination, visual field in technic of isopters and profile quantitative perimetry (meridian retinal thresholds examination) using Kowa automated perimeter. In 15% of examinees we found strictly foveal "degeneration", and changes of visual fields: higher meridian thresholds and typical changes with invagination of isopters. It is very interesting that these children with damaged visual field and fundus picture do not protect their eyes from the sunlight during summertime. We suggest the possibility of the influence of higher sun radiation as one of the risk factors in the earlier development of future AMD.

Long term results of age-related macular degeneration therapy with prednisolone acetate--special refer to peripheral visual field changes.

In the north Croatian Adriatic area in the period of seven years (from January 2001 to September 2007) 475 patients (39 to 80 years of age) with dry form of age related macular degeneration (AMD) were diagnosed. Complete ophthalmologic examination with special reference to visual field testing (Perimetric analysis) was performed. Peripheral visual field defects were found in 85% of patients. Elderly patients with more advanced forms of macular degeneration had more peripheral visual field defects. In 400 patients corticosteroid therapy (5 mg Prednisolonacetate, anterior H-inject, Winthorp) was administered via parabulbar injections every day/five days. Control group consisted of 75 patients treated with regular polyvitamine therapy (Lutein, Beta Karoten, Vitamin E). Patients treated with corticosteroids had peripheral visual field improvements from 10 to 25 degrees and central field improvements from 5 to 20%. In the control group treated with vitamins, central visual field showed improvements from 0.5 to 1% in 43 patients but without peripheral visual field improvements after 6 months.

Dental inflammation and central retinitis--it is important to protect the retina from the harmful sunlight.

During 3-year study of 73 patients with dental inflammation, sinusitis, otitis and 5 cases with granuloma, in 9 cases we observed the development of central retinitis. All patients were medicated with the same antibiotics and parabulbar depo of Prednisolonacetate. To 50% of these patients, we suggested eye protection with Yellow Medical filters during two months. In the first group with medication we observed better vision in 69%, but in the second group with eye protection with Yellow Medical filters we observed normalization of vision in 100%.

Influence of insolation on osteoporosis progression in androgen deprived nonmetastatic prostate cancer patients.

Prostate cancer is a major public health problem in all the developed countries. Increasing numbers of men with nonmetastatic prostate cancer are receiving long-term androgen deprivation therapy (ADT). ADT is associated the loss of bone mineral density and a increased risk of bone fractures. The standard recommendations for male bone health include above all optimizing calcium and vitamin D intake, and exercise. Vitamin D3 is an essential factor in the maintenance of bone health and calcium homeostasis. The main supply of vitamin D3 is obtained through photosynthesis in the skin. The aim of this study was to investigate the influence of insolation on osteoporosis progression in androgen deprived nonmetastatic prostate cancer patients. We divided our androgen deprived prostate cancer patients in 2 groups. The first group (A) consists of 224 patients with insolation rate less then 3 h per week. The second group (B) consists of 174 patients with insolation rate greater then 10 h per week. With a questionnaire we determined, that patients from both groups were 70 to 80 years old, body mass index was 25-30 kg/m2, androgen deprivation was 4-6 years and received no vitamin D supplements. In the group A 21.86% suffered pathologic fractures do to osteoporosis. In the group B 10.92% patients suffered from osteoporotic bone fractures. The risk for pathological bone fractures is significantly greater in the group A. In conclusion higher insolation in androgen deprived nonmetastatic prostate cancer patients significantly decreases the osteoporosis progression and the risk of pathologic bone fractures.

Expression of bone morphogenetic proteins, cartilage-derived morphogenetic proteins and related receptors in normal and osteoarthritic human articular cartilage.

Newborn and adult articular cartilage expresses bone (BMPs) and cartilage derived morphogenetic proteins (CDMPs). These morphogenetic proteins act over membrane receptors (BMPRs). We examined the expression pattern of BMP-7, BMP-3, CDMP-1, CDMP-2 and their receptors in adult normal and osteoarthritic, articular, knee cartilage. Immunostaining was carried out using polyclonal antibodies. The expression of BMP-7,-3, CDMP-1,-2 was detected in all layers of normal articular cartilage with the strongest expression in chondrocytes of the transitional layer. BMP-7 and CDMPs expression decreased in osteoarthritic articular cartilage whereas BMP-3 expression was absent. BMPR-IA and BMPR-II were strongly expressed in both normal and osteoarthritic articular cartilage. BMPR-IB was not expressed in osteoarthritic (OA) cartilage. BMPs and CDMPs with intact signalling play an important role in articular cartilage homeostasis, preventing cartilage degeneration.

Development and progression of age-related macular degeneration after cataract surgery--in the near future it could become a forensic medicine problem.

After testing all types of implanted IOLs with spectrophotometer, author estimated that filtering of sun light is not successful, leaving open the possibility of development of AMD after cataract surgery. This is especially serious problem in implantation of IOLs to children. Until recently, implantation of intraocular lenses without or with inappropriate UV protection was not considered a serious problem. Nowadays we know that, especially in children, such treatment is no longer acceptable and results in AMD. It is only a matter of time when the first lawsuit will appear on it. We suggest obligatory eye protection after cataract surgery (aphakic and pseudophakic eyes) with Medical filters (Yellow-Green: 550-600 nm) and regular ophthalmic controls.

Appearance of age related maculopathy after cataract surgery.

The pathogenesis of age-related maculopathy (ARM), the most common cause of visual loss after the age of 60 years, involves a variety of hereditary and environmental factors. When the cataractous lens is removed and replaced by clear intraocular lens, a significant increase in ocular transmittance of optical radiation occurs. The aim of this study was to assess whether cataract surgery in older persons may increase the risk for development of ARM. This is a retrospective study. Medical records of 307 patients, aged 43 to 96 years, (163 male and 144 female) were randomly evaluated. They had undergone cataract extraction (phacoemulsification or extracapsular lens extraction) with clear intraocular lens implantation from January 2001 to December 2005 at the Department of Ophthalmology, University Hospital Rijeka. Patients were examined two weeks after surgery and followed up for at least two years. Based on the exclusion criteria, only patients without any sign of AMD at the first postoperative check up were included. A total of 80 patients (26%) showed development of ARM at the last check up, which was at least 2 years after surgery. Our results indicate that pseudophakia is a risk factor for development of ARM.

Age-related macular degeneration is not macular process only--peripheral retina is attacked too.

On a small island of Rab, geographical latitude 44 degrees 40' N, with the highest solar radiation among Adriatic islands, 1371 patients were examined in 2003-2005 period, with the aim of estimating the frequency of the patients number with Age-related Macular Degeneration (AMD), and further if the peripheral retina is damaged similarly as the macular region. In the first group of agriculturists and fishermen (n = 1300) we estimated the AMD, initial and middle stage of AMD, in 18% of population, but in urban population only by 2 patients. Perimetric analysis with computerized Kowa perimeter, estimated that the peripheral retina is affected similarly as the macular region. Author concludes that for this reason, the usual term of "Age-related Macular Degeneration" should necessarily be named with the suffix "Peripheral", or "Age-related Retinopathy".

Expression of cell cycle and apoptosis regulatory proteins and telomerase in melanocitic lesions.

To gain insight into the role and association of cell cycle and apoptosis regulatory proteins and telomerase activity in the course of progression of melanocitic lesions we have examined immunohistochemicaly, expression and the distribution of p53, bcl-2, Ki-67 and telomerase in 25 samples of common and dysplastic nevi, and 45 samples of primary invasive melanomas. Protein p53 expression was significantly increased in dysplastic as compared with common nevi and melanomas (p < 0.001). Bcl-2 protein expression was significantly increased in melanomas as compared with common aquired and dysplastic nevi (p = 0.001). Nevi and melanomas exhibited clear-cut differences in terms of Ki-67 expression. Telomerase expression was significantly increased in melanomas as compared with common acquired (p = 0.014) and dysplastic nevi (p < 0.001). Enhanced telomerase activity in association with increased bcl-2 expression in the course of melanoma progression could contribute to development and progression of melanoma.

Histopathological analysis of UV-B irradiated retina by Cavia Coba'ya and with protection of transmission light lambda 550-600 nm.

In 14 experimental Cavia Coba'ya eyes were irradiated with UV-B light, lambda 312 nm, 25 J/cm2 in 15 minute exposure. Including the transmission of light through optical media: cornea, lens, humor aqueous and vitreous body, and pupil surface of 7 mm2, we can calculate that in these conditions retina can be really irradiated with 10 J/cm2. The half number of Cavia Coba'ya was simultaneously irradiated with visible light, lambda of 550-600 nm (1000 Lx). Control group was 5 Cavia Coba'ya. Two months after irradiation, eyes were enucleated and fixed in 4% formaldehyde. Histopathological findings showed alterations of all retinal layers: loss of ganglion cells, axons, reduction of photoreceptors, vacuolar degeneration and hyperplasia of retinal pigment epithelium. In the second group of irradiance, the eyes with visible light lambda 550-600 nm, all retinal alterations were in 50% decreased.

Histopathology of the pterygium in population on Croatian Island Rab.

In the 1975-2004 period, 130 cases of pterygium were estimated, 83 males and 47 females, on a small island Rab. Island Rab is located in the north part of the Adriatic sea, which has very high index of sun radiation. Pterygium is usually histopathologically defined as a hyperplasia of conjunctival tissue, elastoid degeneration of subepithelieum and fragmentation of Bowman's membrane. Our histopathological findings in 73 eyes are following: conjunctiva with neovascularisation, leukocyte margination and subepithelial basophilic degeneration, proliferation of conjunctival tissue, acanthosis and squamous metaplasia, and mucinous elements, focaly present plasma cells, focuses of increased pigmentisation in basal epithelial layers, tenon capsule with edema, diffuse neovascularisation and fragmentation of fibrils. These findings suggest that in severe cases of pterygium histopathologically exists precancerosis. In conclusion, on the basis of these histopathological findings, especially in the Tenon capsule, we suggest that for surgical procedure of pterygium the excision of the Tenon capsule, extensively under pterygium, is necessary.

Ultraviolet sun radiation and incidence of age-related macular degeneration on Croatian Island Rab.

This epidemiological study is completed on island Rab, located in North Adriatic Sea. For this study it is important that Adriatic Sea has one of the highest solar radiations in geographical area of Europe. The aim of this epidemiological study is to estimate correlation between incidence of Age-Related Macular Degeneration (AMD) and exposure of sunlight in two different populations on island Rab. In the first group of population of island Rab, agriculturists and fishermen (n = 1300), incidence of AMD was in 18%, but in urban population only 2.5%. It is very interesting that correlation exists between incidence of AMD and exfoliation syndrome. In the group of chronic exposure to sunlight (agriculturists and fishermen) exfoliation syndrome exists in 28%, but in urban population it has never been seen. The age in both populations was 45-65 years. We can conclude that there is a very significant correlation between chronic exposure to sunlight and appearance of AMD.

Sunlight and incidence of pterygium on Croatian Island Rab--epidemiological study.

The aim of this epidemiologic study, on small island Rab, in North Adriatic Sea, is to estimate correlation between climatic factors, specially chronic exposure to strong visible and UV light, and appearance of pterygium and exfoliation syndrome. In the first group of population which live in a village and who are agriculturists and fishermen (480 persons) appearance of pterygium is in 23% (16% in males and 7% in females), but 0.0% in urban people (61 people). The appearance of exfoliation syndrome was in the first group of agriculturists and fishermen population in 21%, of which 19% of males and 2% of females, and in urban people 0.0%. The higher intraocular pressure in exfoliation syndrome was 92%. All population in this examination were in the highest age (mean age is 65-80 years). Chronic exposure to sunlight caused the high percentage appearance of pterygium and exfoliation syndrome.

Prednisolone neuroprotective therapy in age-related macular degeneration.

134 patients with Age-related Macular Degeneration (AMD) (aging 47-75 years) were treated in therapy procedure with parabulbar injections of Methylprednisolone Acetate and Prednisolone Acetate. In the first group of patients with AMD (n = 71 patients) were treated with Methylprednisolone acetate, and second group (n = 63 patients) with Prednisolone acetate. Each patient was given doses of 60 mg, through two weeks, 10 mg every second day. It's estimated in all patients ameliorate in macular threshold, so that it's in the group with Methylprednisolone treatment, ameliorate effect begins after first week, than in second group, treated with Prednisolone, initial ameliorate effect is after second week. Complete effect in both groups is after 2 months. It can be concluded that the treatment of AMD with glucocorticoids has the ameliorate effect in vision loss and it is decided that earlier effect in the group treated with Methylprednisolone, is probably of higher affinity for glucocorticoid receptors.

Recurrent pleomorphic adenoma of epipharynx following irradiation therapy.

We present a case of a 67-year-old female patient having a pleomorphic adenoma of epipharynx with intact fibrous capsula, which despite its benignity recurred and, moreover, responded quite well to irradiation therapy. The patient, at first, refused any therapy. Three years later, when the CT showed tumor enlargement she accepted only irradiation therapy, resulting in significant reduction of tumor size. Five years later the tumor recurred but without malignant transformation. She still refused surgery, but accepted re-irradiation therapy. After a three-year follow-up the patient has no symptoms of the tumor enlargement. This case shows that the irradiation therapy might be quite effective in the treatment of pleomorphic adenoma of epipharynx, but it is clear that much better results could be accomplished in combination with the surgery. In cases when the surgery is rejected or not possible because of the vicinity of the vital structures, we recommend the irradiation therapy as a therapy of the choice.

Early cancer in congenital choledochal cyst.

We report a case of 35-yr-old woman with early cancer in congenital choledochal cyst. She had a five-year history of intermittent right upper abdominal pain and intermittent jaundice. In this period she had a few abdominal ultrasonographies, but the cholelithiasis had not been found. Now, she was admitted to our hospital because she felt right upper abdominal pain with slight jaundice and subfebrile temperature four weeks ago. Abdominal ultrasonography showed enormous dilatation of the common bile duct, which was suspected as choledochal cyst. Computed tomography and endoscopic retrograde cholangiopancreatography revealed cystic dilatation of extrahepatic bile duct. An anomalous pancreaticobiliary junction was not found. The patient with congenital choledochal cyst was operated on. The excision of choledochal cyst was done with hepaticojejunostomy Roux-en-Y. There were no lymph nodes metastases. On the central part of choledochal cysts mucosa, it was shown a white plain area of thickness 0.3 cm and 0.8 cm in diameter. Histologically it was well-differentiated tubular adenocarcinoma, which was limited to the mucosa and which did not penetrate to other parts of the bile duct wall. From our knowledge, only small number cases of early cholangiocarcinoma in choledochal cyst were until now reported. Nearly eight years after the operation the patient feels very well, and has optimal working ability (Karnofsky 100%).