Eye Tumor Research Articles

Effects of peptides from the secretin family on viability of Y79 retinoblastoma cells

Background Retinoblastoma is an eye tumor arising from retina, with the highest prevalence between 0–4 years of age. The most frequently used retinoblastoma cell lines are Y79 and WERI. Secretin, Pituitary Cyclase Activating Polypeptide (PACAP), Vasoactive Intestinal Peptide (VIP) belong to the secretin family of structurally related peptides. They act through activation of G protein-coupled receptors. VIP and PACAP bind with similar affinities to VPAC 1 and VPAC 2 receptors, whereas PAC1 receptor is preferentially activated by PACAP. Endogenous PACAP is present in two forms: 38-aminoacid and C-terminally truncated PACAP27. Although Y79 cells express functional PAC 1 receptors, nothing is known about role PACAP might play in these cells. This study was aimed at examining effects of secretin family peptides on survival of Y79 cells. Methods Cell viability and mitochondrial function were measured by 3-(4,5-dimethyl-2-thiazolyl)- 2,5-diphenyl-2H-tetrazolium bromide (MTT) reduction to MTT formazan by cellular mitochondrial dehydrogenases following 24, 48 and 72 h incubation with the peptides. Results VIP (0.001–1 μM) did not alter Y79 cell survival. PACAP38 and PACAP6-38 (0.1–5 μM) decreased viability of Y79 cells in a concentrationdependent manner. The cytotoxic effect of both peptides was additive. PACAP27 (0.1–5 μM) reduced cell survival, but the observed effect was markedly weaker than those evoked by PACAP38 and PACAP6-38. Maxadilan (0.1–3 μM), high-affinity PAC1 agonist, did not alter the viability of Y79 cells, but interestingly it enhanced the effect of PACAP38 and PACAP6-38. Similarly, secretin (0.001–3 μM) did not modulate the viability of Y79 cells, but potently increased the suppressive action of PACAP38. Conclusions It is suggested that cytotoxic effects of PACAP38 and PACAP6-38 on Y79 cells result from their interaction with another, non PAC 1 , receptor expressed by these cells. The enhancement of cytotoxic effect of PACAP(s) by secretin and maxadilan may be due to the competitive inhibition of peptidases degrading PACAP or to displacement of PACAP from PAC 1 .

Cystatin C and lactoferrin concentrations in biological fluids as possible prognostic factors in eye tumor development

ObjectivesTo investigate the possible role of cystatin C in eye biological fluids locally and in serum and lactoferrin revealing anti-tumor activity in eye tumor development.BackgroundThe increased number of eye tumors was registered recently not only in the countries with high insolation, but also in the northern countries including Russia (11 cases per million of population). Search for new biological markers is important for diagnosis and prognosis in eye tumors. Cystatin C, an endogenous inhibitor of cysteine proteases, plays an important protective role in several tumors. Lactoferrin was shown to express anti-tumor and antiviral activities. It was hypothesized that cystatin C and lactoferrin could serve as possible biomarkers in the diagnosis of malignant and benign eye tumors.Study designA total of 54 patients with choroidal melanoma and benign eye tumors were examined (part of them undergoing surgical treatment). Serum, tear fluid and intraocular fluid samples obtained from the anterior chamber of eyes in patients with choroidal melanoma were studied.MethodsCystatin C concentration in serum and eye biological fluids was measured by commercial ELISA kits for human (BioVendor, Czechia); lactoferrin concentration – by Lactoferrin-strip D 4106 ELISA test systems (Vector-BEST, Novosibirsk Region, Russia).ResultsCystatin C concentration in serum of healthy persons was significantly higher as compared to tear and intraocular fluids. In patients with choroidal melanoma, increased cystatin C concentration was similar in tear fluid of both the eyes. Lactoferrin level in tear fluid of healthy persons was significantly higher than its serum level. Significantly increased lactoferrin concentration in tear fluid was noted in patients with benign and malignant eye tumors.ConclusionIncreased level of cystatin C in tear fluid seems to be a possible diagnostic factor in the eye tumors studied. However, it does not allow us to differentiate between malignant and benign eye tumors. Similar changes were noted for lactoferrin in tear fluid.

Curcumin and its emerging intraocular benefits

I read with great interest the recent article “Curcumin inhibits proliferation of human lens epithelial cells: a proteomic analysis” by Hu et al. (2012), published in Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology). Curcumin may be of significant benefit in other optic disorders besides cataracts. Curcumin exerts anti-neoplastic effects in eye tumors such as retinoblastomas. It mediates these anti-cancer effects by altering the microRNAs (miRNAs) expression profile. Overall, sixteen miRNAs are down-regulated. Simultaneously five miRNAs, especially miR-22, are up-regulated in the retinoblastomas cells (Sreenivasan et al., 2012). The target gene of miR-22 is erythoblastic leukemia viral oncogene homolog 3 (Erbb3). Curcumin attenuates reactive oxygen species (ROS) levels and thereby affords protection to retinal pigment cells from oxidation injury. These protective effects are mediated by curcumin induced up-regulation of heme oxygenase-1 (HO-1) (Woo et al., 2012). The highest HO-1 expression is seen at a concentration of 15 μmol/L (Mandal et al., 2009). Diabetic retinopathy can be attenuated by curcumin by virtue of its anti-oxidant properties. It also indices hypoglycemia thus proving to be of further benefit in mitigating the development of diabetic retinopathy (Gupta et al., 2011). Curcumin decreases the elevations in vascular endothelial growth factor noted in diabetic retinopathy. Ischemia/reperfusion injury in the retina is attenuated by curcumin administration. It mediates these protective effects by decreasing the activation of signal transducers and activators of transcription 3 (STAT3) (Wang et al., 2011). Simultaneously, activation of nuclear factor-κB (NF-κB) is also inhibited and further augments the protective effects of curcumin. As a result, it decreases vascular as well as neuronal degeneration in the retina. Up-regulation of p-IκBα and MCP-1 is also inhibited. These protective effects are even seen 48 h following the ischemic injury. Curcumin also may be effective in the therapeutic management of retinitis pigmentosa. Retinitis pigmentosa secondary to P23H rhodopsin mutation may especially be amenable to curcumin therapy. Curcumin mediates these effects by decreasing stress on the endoplasmic reticulum and by improving gene expression in the retina as well as by improving retinal morphology (Vasireddy et al., 2011). Curcumin also dissociates protein aggregates and restores the expression of NF-κB thus further improves the pathology in retinitis pigmentiosa. These protective effects are reversed by the application of NF-κB inhibitory peptides. Curcumin is also of benefit in proliferative vitreoretinopathy (Alex et al., 2010). It mediates these effects by inducing caspase 3 dependent apoptosis. Curcumin has an attenuatory effect on Bcl-2 and augments Bax levels (Lu et al., 2009). It also accentuates Fas-associated death domain protein (FADD) and Fas levels at the same time. As a result there is increased G2/M phase arrest. The above examples clearly illustrate the significant benefits of curcumin in intraocular pathologies and the need for further studies in this regard.

Papillary Thyroid Carcinoma: Bilateral Choroidal Metastases with Extrascleral Extension

Here, we present the case of a patient with bilateral choroidal metastases with extraocular extension in one eye. Metastasis of papillary thyroid carcinoma to the uvea is extremely rare, with only 6 patients reported in the literature. A 62-year-old man with a prior history of papillary thyroid carcinoma suffered the rapid loss of vision in his right eye. He had neovascular glaucoma, total retinal detachment, and a solitary choroidal mass. A month later, his left visual acuity also decreased because of a small macular choroidal mass. The right eye was enucleated and a nodular lesion over the sclera representing extraocular extension was observed. This tumor and the intraocular lesion were composed of papillary excrescences and cystic spaces and stained positively for thyroid transcription factor 1 and thyroglobulin, all confirming the diagnosis of metastatic papillary thyroid carcinoma. The tumor in the left eye was successfully treated with diode laser transpupillary thermotherapy. The patient expired within a month as a result of widespread pulmonary metastases. Papillary thyroid carcinoma may metastasize to the uvea bilaterally, cause rapid visual function loss, erode the sclera, and may extend outside the globe similar to choroidal melanoma. This aggressive ocular involvement was associated with a dismal prognosis in our patient.

A case of presumed choroidal metastasis from carcinoid tumor treated by photodynamic therapy with verteporfin

We report a case of metastatic choroidal carcinoid tumor with favorable outcome after photodynamic therapy. A 75-year-old woman was presumptively diagnosed with bilateral choroidal metastases from carcinoid tumor. Although the tumor in the right eye showed a tendency toward rapid expansion and required aggressive treatment to preserve vision, the size was still small and we hesitated to use external-beam radiotherapy because of the risk of radiation retinopathy. Consequently, photodynamic therapy was performed on the right eye, resulting in drastic reduction of the size and height of the choroidal tumor. Good visual acuity was maintained after photodynamic therapy. Photodynamic therapy may be an effective treatment for choroidal metastasis from carcinoid tumor.

Retinoblastoma external beam photon irradiation with a special ‘D’-shaped collimator: a comparison between measurements, Monte Carlo simulation and a treatment planning system calculation

Retinoblastoma is the most common eye tumour in childhood. According to the available long-term data, the best outcome regarding tumour control and visual function has been reached by external beam radiotherapy. The benefits of the treatment are, however, jeopardized by a high incidence of radiation-induced secondary malignancies and the fact that irradiated bones grow asymmetrically. In order to better exploit the advantages of external beam radiotherapy, it is necessary to improve current techniques by reducing the irradiated volume and minimizing the dose to the facial bones. To this end, dose measurements and simulated data in a water phantom are essential. A Varian Clinac 2100 C/D operating at 6 MV is used in conjunction with a dedicated collimator for the retinoblastoma treatment. This collimator conforms a ‘D’-shaped off-axis field whose irradiated area can be either 5.2 or 3.1 cm2. Depth dose distributions and lateral profiles were experimentally measured. Experimental results were compared with Monte Carlo simulations’ run with the penelope code and with calculations performed with the analytical anisotropic algorithm implemented in the Eclipse treatment planning system using the gamma test. penelope simulations agree reasonably well with the experimental data with discrepancies in the dose profiles less than 3 mm of distance to agreement and 3% of dose. Discrepancies between the results found with the analytical anisotropic algorithm and the experimental data reach 3 mm and 6%. Although the discrepancies between the results obtained with the analytical anisotropic algorithm and the experimental data are notable, it is possible to consider this algorithm for routine treatment planning of retinoblastoma patients, provided the limitations of the algorithm are known and taken into account by the medical physicist and the clinician. Monte Carlo simulation is essential for knowing these limitations. Monte Carlo simulation is required for optimizing the treatment technique and the dedicated collimator.

Head and Neck: Retinoma

Note Retinoma is the benign precursor to the childhood eye tumor, retinoblastoma. In rare cases, it remains benign for the lifetime of the individual, never progressing to retinoblastoma. Retinoma has three (3) characteristic clinical features: a grey, translucent mass in the retina; cottage cheese-like calcification; and a hyperplastic retinal epithelium/chorioretinal scar (Gallie et al., 1982). Vitreous seeds have also been observed associated with retinoma (Lueder et al., 1995). Clinics and pathology

Lethal metastatic ciliary body melanoma without hepatic disease in a young girl

AbstractPurpose To illustrate a case report of rapid metastatic death due to a ciliary body melanoma in a a young female of 19 years of age, with no hepatic metastatic disease.Methods A young algerian girl was send for conservative treatment for a ciliary body tumor of the left eye on the 19th of march 2012.This eye was blind, with a white cataract.Rubeosis iridis was present on the whole iris surface with total angle closure ,ocular pressure was 41 mm and US showed a temporal ciliary body tumor of 3.5 mm in height and 10 mm in diameter .Results An enucleation was performed on March 20th , but the patient had to be hospitalized on the same afternoon in Intensive Care Unit for drainage of bilateral pleural effusion, purely inflammatory .Full Body CT Scan has shown brain secondary foci of 3 and 5 mm on both frontal lobes.A nodular lesion of 7 mm was also present on the Fowler lung lobe.The liver was not invaded but massive mesenteric necrotic lesions with peritoneal effusion were found. Surgical biopsy of the mesenteric lesions was done in the General Surgery Unit on March 22nd showing melanoma cells.In the same time the ocular pathologists diagnosis was an epithelioid ciliary body melanoma of 10x10 mm. On April 3rd a pleurodesis was created with pleural biopsies in the Thoracic Surgery Unit.Mesothelial pleural hyperplasia without malignancy sign was diagnosed.A chemotherapy with Muphoran has been advised by oncologists and begun soon after she returned in her country where she died at the end of May .Conclusion Death by metastatic disease can also occur without detectable hepatic lesions by US or CT Scan in case of severe ciliary body melanoma.The mechanism of responsible mesenteric lesions for death in the hepatic vicinity has to be explained.

Histologie bei bilateral asymmetrischem vasoproliferativem Tumor der Retina

We present a case of a bilateral vasoproliferative tumor of the retina in a young man. The first symptom was visual impairment due to vitreous hemorrhage. The right eye showed small tumors which were successfully treated by repeated cryocoagulation, photocoagulation and bevazicumab injection. The tumor in the left eye was larger and eventually led to a painful secondary glaucoma. After enucleation, this tumor was examined histologically and immunohistochemically. The clinical and histological differential diagnoses and therapeutic options are discussed.

Poster - Thur Eve - 52: Clinical use of nanoDots: In-vivo dosimetry and treatment validation for stereotactic targets with VMAT techniques.

A newly acquired nanoDot In-Light system was compared with TLD-100 dosimeters to confirm the treatment dose in the multiple cases: an electron eye treatment, H&N IMRT and VMAT validation for small targets. Eye tumour treatment with 9 MeV electrons A dose of 1.8 Gy per fraction was prescribed to the 85% isodose. The average dose measured by three TLDs and three Dots was 1.90 and 1.97 Gy. Both detectors overestimated dose, by 2.9% and 6.7% respectively. H&N IMRT treatment of skin cancer with 6 MV photons Dose per fraction is 2.5 Gy. The average doses measured by two TLDs and two Dots were 2.48 and 2.56 Gy, which represent errors of -0.8% and 2.2%, respectively. VMAT validation for small targets using an Agarose phantom, dose 15 Gy A single-tumour brain treatment was delivered using two coplanar arcs to an Agarise phantom containing a large plastic insert holding 3 nanoDots and 4 TLDs. The difference between the average Pinnacle dose and the average dose of the corresponding detectors was -0.6% for Dots and -1.7% for TLDs. A two-tumour brain treatment was delivered using three non-coplanar arcs. Small and large plastic inserts separated by 5 cm were used to validate the dose. The difference between the average Pinnacle dose and the average dose of the corresponding detectors was the following; small phantom 0.7% for Dots and 0.3% for TLDs, large phantom-1.9% for Dots and -0.6% for TLDs. In conclusion, nanoDot detectors are suitable for in-vivo dosimetry with photon and electron beams.

SU-E-T-517: Characterization of Relative Doses and Source Strengths for Various Plaque Sizes and Tumor Dimensions in the Treatment of Uveal Melanoma.

To characterize the relative doses and source strengths for various eye plaque sizes and tumor dimensions in the treatment of uveal melanoma. Several tumors with basal diameters ranging from 6-16mm and apical height of 5-10mm were planned using the Pinnacle3 treatment planning system following the American Brachytherapy Society's recommendations. The data is based on 5-day implant to deliver 85Gy with a dose rate of 70.9cGy/hr. Choice of plaque size is based on a 2-3 mm margin on either side of the tumor. Doses to the fixed locations: sclera, center of the eye and opposite sclera were obtained. From our results we see larger source strengths needed for smaller plaques due to smaller number of sources used. The exception is with 14mm and 16mm plaques containing the same number of sources where the 16mm plaque has slightly higher source strengths. For both the inner and outer sclera, the relative dose increases with increasing height. For a 12mm plaque, the relative dose of the outer sclera increases from 4-10 times that of the Rx dose at the apex of the tumor. For a 20mm eye plaque, the relative dose of the outer sclera increases from 2-5 times that of the prescription dose at the apex of the tumor. As apical height increases, the relative dose at the center of the eye increases to about 75% of the Rx dose at 10cm depth for all plaque sizes. At the inner sclera surface opposite the center of the tumor base the relative dose is 20-22% of the Rx dose for all plaque sizes. The data provided will be a helpful tool in evaluating and predicting complications in the retina and sclera based on the tumor dimensions and selected plaque size.

Disseminated tumour cells in bone marrow of patients with uveal melanoma

Approximately 50% of patients with uveal melanomas develop metastases. Thus, it is important to improve our understanding of how melanoma metastases develop. As part of a uveal melanoma micrometastasis study, we compared the detection rates of immunomagnetically selected (IMS) tumour cells in bone marrow (BM) with positively stained tumour cells using immunocytochemistry (ICC). Bone marrow mononuclear cells were isolated. Immunocytochemistry cytospin preparations were immunocytochemically stained in parallel with two different melanoma antibodies, 9.2.27 and HMB45. Using IMS, melanoma cells were selected from BM mononuclear cell fractions using immunomagnetic beads coated with the 9.2.27 antibody and identified by light microscopy. In cytospin preparations from 226 patients, melanoma cells were detected in 24 (10.6%), 10 with 9.2.27 and 17 with the HMB45 antibody. In three cases, we found positive cells with both antibodies. Six of the 226 (2.6%) patients that stained positively with ICC died with metastatic disease, all also positive with IMS. Sixty-six (29.2%) patients had positive BM samples with IMS at the first examination. Immunomagnetic selection (IMS) was positive in 36.8% of the 57 patients who later developed clinical metastases. Twenty-one IMS-positive patients and 31 IMS-negative patients died of metastases, in total 52 of 226 patients (23.0%). The mortality rate of melanoma metastasis was 24% (6/24) after at least 4 ½ years in ICC-positive patients compared to 38.5% (20/52) in IMS-positive patients. The presence of melanoma cells in BM of patients with uveal melanoma is documented in our study with IMS and ICC. Immunomagnetically selected is more sensitive than ICC in detecting tumour cells in BM. However, statistically, we did not find any prognostic impact of the presence of melanoma cells in BM.

Are children born after infertility treatment at increased risk of retinoblastoma?

Retinoblastoma (RB) is the most frequent eye tumour in children, with an incidence of 1 in 15-20,000 births. It accounts for 11% of all cancers in the first year of life. Except for the hereditary forms, its causes are not well-known. Studies have recently suggested an increased risk of RB among children born after IVF, but the relevant literature is sparse. We assessed the association between infertility treatment, subfertility and RB. We included all children living in France diagnosed with RB between 1 January 2000 and 31 December 2006 at the Institut Curie, the national reference centre for RB diagnosis and treatment. We used multiple logistic regression to compare them with a national sample of births in France in 1998 and 2003 (n = 28 170). The study included 244 non-familial RB cases. The risk of RB increased with maternal age [adjusted odds ratio (adj OR) = 2.07, 95% confidence interval (CI) 1.33-3.22 at 35-39 years compared with younger than 25 years and adj OR = 2.42, 95% CI 1.22-4.81 at 40 years or older], but the associations with IVF (adj OR = 1.37, 95% CI 0.64-2.95) and ovarian stimulation or intrauterine insemination (adj OR = 1.35, 95% CI 0.77-2.38) were not statistically significant after adjustment for maternal age and tobacco use. Among women who had no infertility treatment, the risk of RB was significantly increased when time to pregnancy exceeded 24 months (adj OR = 2.02, 95% CI 1.17-3.48) compared with time to pregnancy ≤ 24 months. Our study did not observe a significantly increased risk of RB associated with infertility treatment, in particular with IVF. But we did find an increased risk for women for whom time to pregnancy exceeded 24 months.

Abstract 1826: Anti-tumorigenic effects by targeted functional disruption of the Sin3 PAH-2 domain

Abstract The Sin3 A/B adapter proteins function as structural scaffolds for repressor/activator complexes that regulate transcription through the specific association with histone modifying enzymes and a number of transcription factors. Sin3 contains four paired amphipathic α-helices (PAH domains). We have reported earlier that targeted disruption of the PAH2 domain with a SID (Sin3 Interaction Domain) peptide decoy in triple negative (TN) breast cancer cells leads to cytoskeletal reorganization, loss of anchorage independent growth and 3D invasive morphology and decreased cell adhesion and invasion. There is epigenetic reprogramming of silenced genes such as CDH1, ESR1 and RARA which are re-expressed and together contribute to a SID decoy induced switch from basal to a more differentiated luminal phenotype (Farias, et. al., PNAS, 2010, 107:11811-6). Computerized screening coupled with such assays as Duolink, GST pull downs and mammalian two hybrid identified small molecule inhibitors (SMI) that mimic the effects of the SID decoy peptide. SMI inhibit cellular invasion at nanomolar range and in in vivo mouse myc TN breast cancer prolong latency, decrease local invasion and metastasis. Tumors recovered showed evidence of re-expression of E-cadherin and estrogen receptor. Early effects of SID decoy in TN breast cancer cells include inhibition of invasion that is associated with a significant decrease in Src phosphorylation within 2-4hr of treatment. Recovery of phosphorylation after SID decoy washout is coupled with recovered invasion at 24hr. These effects occurred prior to measurable increase in E-cadherin expression, suggesting a non-transcriptional effect. In Drosophila larval breast cancer models with activated Src/Ras, overexpression of SID inhibited (60%) tumor growth in the eye imaginal disc, and was eradicated by the addition of a MEK inhibitor (AZD-6244), indicating a strong synergy between SID and AZD-6244. In the adult fly SID expression greatly inhibited RetMEN2B induced eye tumors (90%). These data demonstrate that SID decoys have a potential to be effective agents in the treatment of TN breast cancer by promoting basal phenotype reversal, inhibiting invasion and metastasis, and could be synergistic with specific inhibitors of signal transduction targets. Moreover, SID decoys can overcome profound oncogenic stimulus such as Ras, Src and Ret suggesting that they have a potential greater role than just in the treatment of TN breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1826. doi:1538-7445.AM2012-1826

Little known ophthalmic interests of Emil von Behring, the first Nobel Prize Laureate in Medicine or Physiology

Although the work for which Emil von Behring (1854-1917) was awarded the first Nobel Prize Winner for Medicine or Physiology in 1901 was on serum therapy, not only was he trained and worked as an ophthalmologist but he also wrote his doctoral dissertation on a practical ophthalmological topic whilst in Berlin under Carl Schweigger (1830-1905). He later worked for 3 years as an assistant and co-worker with the famous Polish ophthalmologist Boleslaw Wicherkiewicz (1847-1915), in Poznan where he described an interesting ophthalmic case in a scientific journal. His life and work in other fields have been well studied, but his interests and relationship to ophthalmology that played an important role in, at least part of, Behring's life have never previously been analysed thoroughly.

A Tandetron™ as proton injector for the eye tumor therapy in Berlin

The therapy of eye tumors with fast protons is an excellent tool giving very high local control rates. At the Helmholtz-Zentrum Berlin (HZB) almost 1800 patients were treated since 1998. A 2 MV Tandetron™ was installed as injector for the k = 132 HZB cyclotron. Using the standard 358 duoplasmatron ion source with direct extraction of negative hydrogen ions an extremely stable proton beam can be delivered, both on the short-term and the long-term scale. The hair-needle filaments made from thoriated tungsten wires have safe operation times of more than 1000 h.

Investigation of different operating modes of ultrasonic annular array used in ophthalmology

The early-stage diagnosis of malignant tumours in eye is very important in ophthalmology in order metastasis of cancer could be prevented and the human life could be saved. Ultrasonography of eye is used already for some time and as it possesses no risk to a patient health it can be repeatedly performed for following of the disease progression. In order to get as much as possible valuable information about the tumours and their structure it is necessary to create new methods and instruments for extraction of qualitative and valuable information from the received ultrasonic signals. In order to overcome limitations of the existing equipment the new knowledge concerning interaction of ultrasonic waves with intraocular tissue and back-scattering from the tissue affected by the tumour are necessary to be collected. For example, for optimization of the design and operation performance of ultrasonic annular arrays, numerical simulation can be performed. The objective of this research was to investigate using CIVA software different possibilities of beam focusing in eye using on ultrasonic annular array and to find the optimal solution, which can be used in practice. The ultrasonic fields focused at different distances from the transducer are presented. The propagation of the ultrasonic wave in the eye with tumour and without has been simulated. The simulated and experimental B-scans of the healthy eye and the eye affected by tumour are presented as well. The presented results demonstrate that it is possible to locate malignant tumours in the eye using the optimised ultrasonic annular array.http://dx.doi.org/10.5755/j01.u.66.4.1027

A pathologic review of ophthalmic tumors in Kano, Northern Nigeria

Background and Objective: Tumors of eye and ocular adnexa are reported to be common in Africa, but no formal study has been conducted here in Kano, the largest Northern Nigerian city. This study is a documentation of the pattern of ophthalmic tumors in our locality. Materials and Methods: This was a 12-year (1999-2010 inclusive) retrospective study of all orbito-ocular neoplasms diagnosed at the pathology department of a teaching hospital. Results : 438 ophthalmic tumors were diagnosed during the study period, of which 79.7% were malignant and 20.3% benign. Males were slightly more preponderant with M/F ratio of 1.3:1. Retinoblastoma and conjunctival squamous carcinoma were the commonest tumors respectively comprising 44.5% and 18.9%. These two ocular malignancies also largely accounted for the bimodal age distribution peaks of ophthalmic cancer in the 1 st and 4 th decades. Conjunctival squamous papilloma and hemangioma were the most prevalent benign ophthalmic tumors. Conclusion : Our findings were broadly similar to most other Nigerian and African studies but significantly at variance with those of the western world.

Role of Pigment Epithelium-Derived Factor in Stem/Progenitor Cell-Associated Neovascularization

Pigment epithelium-derived factor (PEDF) was first identified in retinal pigment epithelium cells. It is an endogenously produced protein that is widely expressed throughout the human body such as in the eyes, liver, heart, and adipose tissue; it exhibits multiple and varied biological activities. PEDF is a multifunctional protein with antiangiogenic, antitumorigenic, antioxidant, anti-inflammatory, antithrombotic, neurotrophic, and neuroprotective properties. More recently, PEDF has been shown to be the most potent inhibitor of stem/progenitor cell-associated neovascularization. Neovascularization is a complex process regulated by a large, interacting network of molecules from stem/progenitor cells. PEDF is also involved in the pathogenesis of angiogenic eye disease, tumor growth, and cardiovascular disease. Novel antiangiogenic agents with tolerable side effects are desired for the treatment of patients with various diseases. Here, we review the value of PEDF as an important endogenous antiangiogenic molecule; we focus on the recently identified role of PEDF as a possible new target molecule to influence stem/progenitor cell-related neovascularization.

The Epigenetic Origin of Retinoblastoma

The aim of the present review is to give new insights into the pathogenesis of retinoblastoma, by applying the principles of epigenetics to the study of clinical, epidemiological and biological data concerning the disease. As an emerging new scientific approach linking the genome to the environment, epigenetics, can not only explain the inconsistencies of the mutational (‘two hit’) model in the genesis of retinoblastoma, but also open new outstanding scenarios in the fields of diagnosis, treatment and prevention of this eye tumour and cancer in general. After more than four decades of predominance of the ‘genetic’ theory, this review represents, to the authors’ knowledge, the first attempt to look at retinoblastoma from the point of view of epigenetics. The epigenetic model in the genesis of retinoblastoma, proposed herein, emphasises the role of environment and its interactions with the genome, in generating retinoblastoma in young children. Environmental toxicants, including, among others, radiations, wrong diets and infectious diseases, all play a major role in conditioning the degree of DNA methylation (one of the leading mechanisms of epigenetic gene regulation) in embryos and foetuses during pregnancy, thus leading to stable, functional alterations of the genome, which can be transmitted from one generation to the next, thus mimicking a hereditary disease. An accurate analysis of the currently available literature on both retinoblastoma and epigenetics, coupled with the knowledge of the variegated phenotypic expression of the disease, can easily lead to the conclusion that retinoblastoma is an epigenetic, rather than a genetic disease.