Inhibitory effect of certain neuropeptides on the proliferation of human retinal pigment epithelial cells.

AIMS: To define the effect of the neuropeptides substance P, calcitonin gene related peptide, vasoactive intestinal polypeptide, neuropeptide Y, and secretoneurin on the proliferation of human retinal pigment epithelial (RPE) cells. METHODS: ARPE-19 cells were used. The cells were cultured in Dulbecco's modified Eagle's medium. 1000 and 2000 cells were incubated with the peptides for 3 and 5 days, and the effect of the peptides was evaluated by an ATP lite assay dose dependently. Furthermore, specific antagonists at 10(-6) M were used to find out whether the effect would be reversed. RESULTS: In brief, each of the peptides tested had an inhibiting effect. This inhibiting effect was weak but highly significant, averaging 10% to 15%, and was most pronouncedly seen at concentrations between 10(-10) M and 10(-14) M. Each antagonist reversed the inhibiting effect fully. CONCLUSIONS: These results clearly indicate that RPE cells are under neural control and the low effective concentration of the peptides may be the one physiologically acting on these cells. The results are of important relevance both physiologically and pathophysiologically: physiologically, the inhibitory effect may mean that these peptides cause the cells to remain in a differentiated condition. Pathophysiologically, the findings are relevant in proliferative vitreoretinopathy where RPE cells proliferate in excess. The authors hypothesise that the inhibiting effect diminishes when these cells are swept out and actively migrate from their physiological location and thus, dedifferentiate and begin to proliferate. This hypothesis improves the knowledge of the initial processes in the pathogenesis of the disease as there seems to be a discrepancy between facilitatory and inhibitory influences favouring the former in proliferative vitreoretinopathy. Furthermore, these neuropeptides constitute the first endogenous inhibitors of RPE cell proliferation.

Intraocular lens power calculation after decentered photorefractive keratectomy.

A 59-year-old patient who had photorefractive keratectomy (PRK) to correct high unilateral myopia developed a progressive nuclear cataract. Phacoemulsification and intraocular lens (IOL) implantation were performed. However, determination of IOL power using automated keratometry and computerized videokeratography was not successful in this case of high axial myopia because of a decentered ablation zone, resulting in too-steep keratometric readings. Postoperative hyperopia could only be corrected by an IOL exchange. Because it may not be possible to determine the exact keratometric values for IOL calculation after PRK, subtracting the change in refraction induced by PRK from the preoperative keratometric readings might have been more accurate in this patient.

Substance P in proliferative vitreoretinopathy: the significance of aqueous humor levels for evolution of the disease.

PURPOSE: We detected aqueous humor levels of substance P in patients with various grades of proliferative vitreoretinopathy and with uncomplicated rhegmatogenous retinal detachment. To evaluate the significance of the concentration of substance P at the time of surgery for retinal detachment for subsequent development of proliferative vitreoretinopathy, the latter patients also underwent fundoscopic control examination. METHODS: Using a highly specific and sensitive radioimmunoassay, the content of substance P in fresh samples of aqueous humor obtained by paracentesis was determined both in cataract controls and in patients with uncomplicated rhegmatogenous retinal detachment and with various grades of proliferative vitreoretinopathy. Retinal detachment patients underwent fundoscopic control examination 6 months after surgical reattachment. RESULTS: The mean concentration of substance P in cataract controls was 40.3 (+22.4) fmol/mg protein, in the retinal detachment group 61.9 (+/-13.9) fmol/mg protein and in proliferative vitreoretinopathy 335.2 (+/-24.8) fmol/mg protein, but no correlation between levels of the peptide and various grades of the disease was observed. Already at surgery for retinal detachment three in four patients who developed proliferative vitreoretinopathy presented with levels of substance P in the range of the disease. CONCLUSION: The concentration of substance P in aqueous humor is significantly high in patients with proliferative vitreoretinopathy in whom surgery is indicated. Furthermore, elevation of the peptide in retinal detachment that originates most obviously from a neurogenic mechanism may indicate initiation of processes associated with proliferative vitreoretinopathy, thus representing an indicator of significant risk for evolution of the disease at a very early time.

[Progressive corneal ectasia after laser in situ keratomileusis (LASIK)]. / Progressive Keratektasie nach Laser-in-situ-Keratomileusis (LASIK).

BACKGROUND: LASIK (Laser in situ keratomileusis) is used in refractive surgery especially for correction of higher degrees of myopia. Preservation of Bowman's layer as well as less postoperative pain and the slight to absent subepithelial haze are regarded as advantages compared to photorefractive keratectomy (PRK). However, numerous serious complications have been described in the literature. PATIENTS AND METHODS: LASIK treatment was performed elsewhere in two patients to treat myopia or myopic astigmatism between -6 and -9 diopters (D). An astigmatism of -6 D was corrected with the LASIK method in another patient with keratoconus. Progressive corneal ectasia of up to seven diopters occurred in all four eyes within a few months. CONCLUSION: Corneal ectasia can occur after LASIK even in low degrees of myopia of less than ten diopters. Recently, -12 D has been specified as the upper limit for this technique. It is especially important to rule out an early keratoconus or a forme fruste of keratoconus preoperatively since keratectasia with particularly rapid progression can occur in such cases: we would like to designate this as "malignant keratoconus".

Susceptibility of human retinal pigment epithelial cells to different viruses.

BACKGROUND: Different viruses have been reported to be involved in retinal diseases in animal systems. In humans, herpes simplex virus and cytomegalovirus have been found to cause retinal disease. Most of the studied viruses are neurotropic. In this study, the in vitro susceptibility of human retinal pigment epithelial cells (RPEC) to representative members of different groups of human pathogenic viruses was investigated. METHODS: Early cultures of RPE C - after two or three passages - were infected with the following viruses: herpes simplex virus (HSV) type 1, human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV), cytomegalovirus (CMV), adenovirus types 1 and 7, measles virus, parainfluenza virus and coxsackie virus B3. RESULTS: Cultures of RPE C could be infected with neurotropic viruses like HSV or measles virus as well as with typical respiratory viruses like parainfluenza or adenoviruses. Coxsackievirus, an enterovirus, replicated as well as human CMV, whereas EBV and HHV-6, two lymphotropic viruses, failed to infect RPE. CONCLUSION: These findings suggest that a variety of viruses, including those causing rather common illnesses, might be capable of inducing retinal lesions under certain circumstances due to haematogenous spread during the course of viraemia.

Different concentrations of vasoactive intestinal polypeptide in aqueous humor of patients with proliferative vitreoretinopathy and cataract patients.

The pathophysiological events leading to cellular proliferation in proliferative vitreoretinopathy are largely unknown. An involvement of neuropeptides in that disease has recently been discussed, as substance P was found to be highly enriched in the intraocular fluid of patients with proliferative vitreoretinopathy. In the present study, aqueous humor was analyzed for another neuropeptide, vasoactive intestinal polypeptide. Radioimmunoassay revealed significantly increased levels of that polypeptide in the aqueous humor of patients with proliferative vitreoretinopathy as compared with cataract patients who served as controls. As vasoactive intestinal polypeptide contributes to the environment of the retinal pigment epithelial cell layer and induces proliferation of these cells in vitro, this peptide may be involved in the pathogenetic mechanisms leading to cellular proliferation in proliferative vitreoretinopathy.

Elevated levels of substance P in intraocular fluid in proliferative vitreoretinopathy.

Proliferative vitreoretinopathy is the most common reason for failure in retinal reattachment surgery. Since both substance P (SP) and SP receptors were found to be present in the human eye, and as pharmacological studies suggest an importance of SP for ocular functions, we investigated intraocular fluids for the presence of SP in eyes elected for cataract surgery, retinal detachment surgery and retina surgery for severe proliferative vitreoretinopathy (PVR) as well as in eyes with proliferative diabetic retinopathy (PDR). High performance liquid chromatography and radioimmunoassay (RIA) for SP immunoreactivities were performed. The SP mean concentration in intraocular fluid (IOF) of patients for cataract surgery (CS) was 2.2 fmol/ml, for retinal detachment (RD) was 2.7 fmol/ml and for PDR was 1.9 fmol/ml; significantly higher levels (mean concentration of 26.9 fmol/ml) were measured in eyes with PVR. HPLC analysis revealed two immunoreactive peaks coeluting with synthetic SP and SP-sulfoxide, indicating that RIA values represent authentic SP. We conclude that SP may play an important role in PVR. Since SP antagonists are known to inhibit a variety of SP effects in the eye, there might be a useful tool to reveal the importance of SP in this disease and, in this instance, a new possible treatment.

[Data processing at the special diabetes ambulatory center of the Innsbruck Ophthalmology University Clinic--electronic data processing in ophthalmology]. / Datenverarbeitung an der Diabetes-Spezial-Ambulanz der Universitäts-Klinik für Augenheilkunde in Innsbruck--EDV in der Augenheilkunde.

During the last 2 years, a personal computer in the special diabetes department of Innsbruck University Eye Hospital has not merely facilitated statistical analysis; without the PC such analysis would not have been possible. Logistically, the most important function is data acquisition, because the system only works if all data are entered. In addition to data processing, word processing, statistical analyses, and chart processing using graphics software are all done on the PC. The system is currently being developed further to include on-line access to literature databases via Datex-P and additional workstations. After 3 years of experience with the PC it is difficult to imagine doing scientific work without it.

[Spontaneous corneal rupture after strontium irradiation of a conjunctival squamous cell carcinoma]. / Spontane Hornhautruptur nach Strontiumbestrahlung eines Plattenepithelkarzinoms der Konjunktiva.

A 87-year-old female patient with a squamous cell carcinoma of the conjunctiva was treated with local strontium-90 irradiation (with a so-called 'Dermaplatte'). In spite of a relatively low dosage, radiotherapy was followed by a corneal ulcer with consecutive rupture of the cornea. The cause of this unexpected perforation was, besides the effect of low-dose irradiation, probably a metabolic disorder of the cornea and a disturbance of the tear film due to the carcinoma which had spread on Bowman's layer of the cornea in an exophytic manner and was accompanied by a dense lymphocytic infiltration. An exenteration was performed and, at the last examination (1 year later), no local recurrence could be detected.

[Craniofacial surgery]. / Craniofaciale Chirurgie.

Deformities in the orbital area can also be corrected by craniofacial surgery. Early surgery within the first year of life is indicated in cases with intracranial pressure if permanent damage to the eye is to be avoided. Otherwise, corrective surgery should be performed in early childhood, although it can also be performed on adult patients. More severe strabismus cannot be treated, but disturbance of lid function can be positively influenced. From the esthetic point of view considerable improvement can be achieved. These very protracted operations require intensive interdisciplinary cooperation.

[The importance of scleral buckling based on an example]. / Der Wert einer bulbusumgürtenden Operation anhand eines Beispieles.

The importance of the scleral buckling technique without vitrectomy is discussed with reference to a patient with aphakia, myopia and morning-glory redetachment. In this almost hopeless situation, scleral buckling surgery was performed. The culyx of the periretinal membranes was opened without vitrectomy and in spite of massive vitreous body shrinkage. After surgery the retina attached almost completely and the patient's visual acuity improved from light perception to 0.06. His present condition is illustrated by sketches and photographs of the fundus. The value of the method is emphasized by reference to similar cases. The patient, who also underwent retinal detachment surgery on the fellow eye and had been pensioned, is now following his occupation again.

[Possibilities for ocular vessel coagulation (author's transl)]. / Möglichkeiten der Gefässkoagulation.

Present-day possibilities of influencing pathological ocular vessels using an argon laser are presented. A distinction is made here between indirect methods such as area coagulation and direct methods with which specific vessels are treated. Whereas clinical tests involving vessel coagulation with pigmented epithelium absorption have already been carried out more or less successfully, selective vessel coagulation with hemoglobin absorption is still largely at the experimental stage. Our own experiments on animals have shown, however, that with the selection of a suitable coagulation technique and the use of suitable exposure parameters, vessel occlusion can be induced with the argon laser. To achieve this, shortening of the exposure times is particularly necessary.

[The histological structure of peripheral cystoid degeneration in senile retinoschisis (author's transl)]. / Zur Pathogenese äusserer Schichtlöcher in seniler Retinoschisis.

In peripheral cystoid degenerations as the precursor of senile retinoschisis basement membrane material and collagen fibrils are formed; after retinal splitting this newly formed material together with ruptured tissue columns build up a layer on the inner surface of the outer wall of the retinoschisis which tends to shrinkage. This mechanism leads to hole formation in the outer wall; the holes consequently enlarge by a curling inward of the edge of the defect.

[Scanning electron microscopy of cystoid degeneration in the peripheral retina (author's transl)]. / Hohlraumbildungen in der Netzhautperipherie im rasterelektronenmikroskopischen Bild

Scanning electron microscopy of peripheral cystoid degenerations of the retina as well as of reticular or inner cystoid degenerations shows tunnel-shaped and vault-like cavities which are supported by columns. In marked cases of PCD, fibers of a collagenous nature surround and connect the columns. Inside the columns there are cable-like strands, which are probably stretched neuronal processes. The surface covering of the columns is formed as a porous layer. The columns of the reticular cystoid degeneration are thinner and located in processes of the outer columns. Globular structures persent in both systems of are interpreted as deformed erythrocytes.

[Retinoschisis and detachment (author's transl)]. / Retinoschisis und Ablatio

Senile retinoschisis was found in 30 out of 315 pairs of eyes taken from cadavers. The retinal splitting occurred primarily as a result of the confluence of peripheral cystoid degeneration (Blessig's spaces or Iwanoff's cysts). There is no reason to suppose that two different forms of retinoschisis are present if the vessels are located in the inner layer. Based on reticular cystoid degeneration, there was only once case which could have represented another types of splitting. Here the vessels were located in the outer layer; the inner layer consisted only of the vitreous membrane. External spaces in the layer are the main causal factor for the development of retinoschisis detachment.