Substance P and vasoactive intestinal polypeptide in the streptozotocin-induced diabetic rat retina.

PURPOSE: Little knowledge exists about how neurotransmitters behave in the diabetic retina. In this study, the authors measured the concentration of two neuropeptides, substance P and vasoactive intestinal polypeptide, in the streptozotocin-induced diabetic rat retina in a time-dependent manner. METHODS: The retinas of 1-, 3-, 5-, 8-, and 12-week diabetic rats were processed using a highly sensitive radioimmunoassay for both substance P and vasoactive intestinal polypeptide. Furthermore, the peptide-immunoreactivities were characterized by high-pressure liquid chromatography. RESULTS: Substance P and vasoactive intestinal polypeptide were found to be significantly reduced with a maximum decrease of 28.6% (+/-6.7) and 64.5% (+/-10.7) after 5 weeks, respectively. The peptide-immunoreactivities were found in a major peak coeluting with the synthetic peptides indicating that the quantitative values measured by radioimmunoassay represent the authentic peptides. CONCLUSIONS: The reduction of substance P and vasoactive intestinal polypeptide is in clear contrast to the amino acid transmitters GABA and glycine, which have been shown to be elevated in this early stage of diabetic retinopathy. This finding is important for three reasons: First, the decrease may result in reduced excitability of inner retinal neurons, as both peptides are known to modulate the excitability of these neurons; second, the decrease may be the consequence of a depressing and/or damaging effect by excitotoxins; and third, it may help explain why neovascularizations do not occur in this animal model, although VEGF is massively upregulated, as substance P is a very potent vascular growth factor.

The effect of streptozotocin-induced diabetes mellitus on substance P and calcitonin gene-related peptide expression in the rat trigeminal ganglion.

Substance P (SP) and calcitonin gene-related peptide (CGRP) constitute the main sensory peptides in the trigeminal ganglion (TG). The objective of this study was to characterize peptidergic changes in the streptozotocin-induced diabetes mellitus rat model both quantitatively and qualitatively. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (65 mg/kg) and the levels of SP and CGRP were measured by means of radioimmunoassay (RIA) in a time-dependent manner. Peptide immunoreactivities were characterized by high pressure liquid chromatography (HPLC). The expression of both neuropeptides was examined 5 weeks after streptozotocin injection using in situ hybridization with 35S-labelled oligonucleotides. Saline-injected rats served as controls. SP was significantly decreased in the diabetic rat TG, i.e. , a 44.6% (+/-10.9) decrease after 1 week, 40.2% (+/-11.8) after 3 weeks and 72.3% (+/-14.6) after 5 weeks. CGRP was decreased only after 5 weeks (19.6% decrease +/-3.9), whereas at later stages, both peptide levels returned to normal values. HPLC revealed one major peak coeluting with the synthetic peptides. By using in situ hybridization, a significantly increased signal of both peptide-encoding mRNAs was found (43.8%), which seems to act to restore a diabetes-associated depletion of neuropeptides in the diabetic rat TG. The decreased SP- and CGRP levels in the diabetic rat TG reflect a diabetes-associated deficit which may be clinically relevant. Diabetes mellitus is associated with a variety of ocular complications, even corneal complications, including decreased corneal sensitivity, which in many ways resemble those after interruption of the normal trophic innervation of the eye. Our results point to reduced availability of neuropeptides for corneal innervation and may thus support the idea of a partial loss of trophic influences from the trigeminal nerve in diabetics.

[Bilateral panuveitis with serous retinal detachment]. / Bilaterale Panuveitis mit seröser Amotio retinae.

HISTORY: A 45-year-old patient with cat scratch disease presented with bilateral panuveitis as well as bilateral serous detachment of the retina. The patient had suffered from influenza with swollen lymph nodes 2 weeks previously. DIAGNOSIS: The diagnosis could be made serologically: IgG and IgM antibodies against Bartonella henselae were highly positive in the immunofluorescence test and the values for inflammation were also strongly increased. THERAPY: A macular star developed during the course, more in the left eye than in the right eye. The patient was treated with a sulfonamide (Bactrim forte) and prednisolonacetate (Urbason), which was changed to doxyzycline (Doxybene) after an allergic reaction developed. Clinical findings were reduced significantly and visual acuity improved. CONCLUSIONS: Bartonella henselae should be excluded when panuveitis occurs with serous retinal detachment. A uveitis anterior could precede this occurrence.

Influence of serum lipid fractions on the course of diabetic macular edema after photocoagulation.

The influence of serum lipid fractions [triglyceride, cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol] on the visual outcome after central laser photocoagulation of 39 patients (65 eyes) with clinically significant macular edema was investigated in a prospective study. Referring to normal Austrian serum lipid levels, the patients were classified into a normal and a pathological group for each of the 4 lipids. Concerning triglycerides and HDL cholesterol, the normal group (triglyceride < 2.29 mmol/l, HDL cholesterol > 1.3 mmol/l) showed a statistically significantly better visual outcome than the pathological group. Also, patients with normal total cholesterol and LDL cholesterol values tended to achieve better results after treatment. We therefore conclude that serum lipid fractions may influence not only the success of laser treatment but also the course of diabetic macular edema.

Grid pattern photocoagulation for diabetic macular edema--long-term visual results.

The authors reviewed the data of 226 eyes in 124 patients with clinically significant diabetic macular edema treated by grid pattern photocoagulation from 1986 to 1994 at the Ophthalmological Clinic of Innsbruck University Hospital. On the basis of baseline visual acuity (VA), eyes were classified in four groups: group 1 = VA < 0.1; group 2 = VA 0.1-0.2; group 3 = VA > 0.2-0.5; group 4 = VA > 0.5. The development of VA from the baseline examination until the last checkup in treated eyes is reported. This classification showed a better visual outcome after photocoagulation in eyes with a decreased VA at baseline (groups 1, 2) compared with eyes with a good initial VA (groups 3, 4). The difference in visual outcome between the second and third groups as well as between the third and fourth groups was statistically significant (p < or = 0.001). A correlation of initial VA with visual outcome after treatment was demonstrated (R = -0.558; p = 0.0001). Clinical conclusions of these results are discussed.

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.

Retinal thickness analysis in subjects with different refractive conditions.

PURPOSE: The aim of the present study is to evaluate a measure of retinal thinning at the posterior pole in eyes with increasing axial myopia. METHODS: 129 eyes of 79 healthy persons with different refractive conditions were examined using a commercially available prototype of retinal thickness analyzer. RESULTS: Increasing myopia has been found to be accompanied by bulbus elongation, and calculation of the values obtained with the instrument revealed a significant decrease in retinal thickness at the posterior pole in eyes with increasing axial myopia, i.e. 4.8 microm/spherical equivalent in the foveolar region and 6.6 microm/spherical equivalent in the other areas of the posterior pole. CONCLUSION: Our data show retinal thinning at the posterior pole in myopic eyes based for the very first time on in vivo measurements. Furthermore, our findings might influence measurement data for other purposes, if the degree of myopia is not taken into account.

Elevated levels of calcitonin gene-related peptide in aqueous humor of patients with proliferative vitreoretinopathy.

PURPOSE: To detect the levels of the sensory peptide calcitonin gene-related peptide in aqueous humor of patients with proliferative vitreoretinopathy and to compare them with those of uninflamed eyes (cataract and uncomplicated rhegmatogenous retinal detachment). MATERIALS AND METHODS: Using a highly specific and sensitive radioimmunoassay the concentration of calcitonin gene-related peptide was detected in fresh samples of aqueous humor obtained via paracentesis. Furthermore, calcitonin gene-related peptide-like immunoreactivities were characterized by high-pressure liquid chromatography. RESULTS: The mean level of calcitonin gene-related peptide was 6.11 fmol/ml in cataract controls and 14.77 fmol/ml in uncomplicated rhegmatogenous retinal detachment. In the cataract group, 9 of 18 cases were below the detection limit and in the retinal detachment group, 5 of 16. In proliferative vitreoretinopathy, the peptide averaged 76.92 fmol/ml and none of the samples was below the detection limit. High-pressure liquid chromatography revealed one major peak corresponding to synthetic calcitonin gene-related peptide. CONCLUSION: In recent studies, we found elevated levels of the sensory peptide substance P in aqueous humor of patients with proliferative vitreoretinopathy. This fact and the present result, the elevation of calcitonin gene-related peptide in aqueous humor of eyes with proliferative vitreoretinopathy, clearly point to an involvement of sensory peptides in the pathobiology of the disease. The source of the elevation is not clear, but we hypothesize that it originates from a neurogenic mechanism, i.e. an acceleration of the peptides by their enhanced release from the iris/ciliary body complex subsequent to sensitization of sensory neurons, thus representing a very interesting epiphenomenon of proliferative vitreoretinopathy. Our results constitute novel aspects in the pathophysiological concept of proliferative vitreoretinopathy and extend the knowledge about the pathobiology of the disease process.