Osteochondritis dissecans (OCD), an endoplasmic reticulum storage disease?: a morphological and molecular study of OCD fragments.

Osteochondritis dissecans (OCD) fragments, cartilage and blood from four patients were used for morphological and molecular analysis. Controls included articular cartilage and blood samples from healthy individuals. Light microscopy and transmission electron microscopy (TEM) showed abnormalities in chondrocytes and extracellular matrix of cartilage from OCD patients. Abnormal type II collagen heterofibrils in "bundles" and chondrocytes with abnormal accumulation of matrix proteins in distended rough endoplasmic reticulum were typical findings. Further, Von Kossa staining and TEM showed empty lacunae close to mineralized "islands" in the cartilage and hypertrophic chondrocytes containing accumulated matrix proteins. Immunostaining revealed: (1) that types I, II, VI and X collagens and aggrecans were deposited intracellulary and (2) co-localization within the islands of types I, II, X collagens and aggrecan indicating that hypertrophic chondrocytes express a phenotype of bone cells during endochondral ossification. Types I, VI and X collagens were also present across the entire dissecates suggesting that chondrocytes were dedifferentiated. DNA sequencings were non-conclusive, only single nucleotide polymorphism was found within the COL2A1 gene for one patient. We suggest that OCD lesions are caused by an alteration in chondrocyte matrix synthesis causing an endoplasmic reticulum storage disease phenotype, which disturbs or abrupts endochondral ossification.

Interleukin-2 receptor--targeted therapy by monoclonal antibodies in the rat corneal graft.

A possible selective therapeutic approach to corneal graft rejection will aim at IL-2 receptor-bearing antigen-activated T-lymphocytes with monoclonal anti IL-2R antibodies. In a rat penetrating keratoplasty model (Lewis x Lewis-BN) comparing to controls (median, 8 days), a significant delay of the allograft reaction was achieved by applying a therapeutic dose (15 mg/kg bw) of cyclosporin A (median, 18 days; p < 0.01), an intraperitoneal (1.0 mg/kg bw) (median, 13.5 days; p < 0.05) or a subconjunctival injection of IL-2R mab (0.5 mg/kg bw ART-18) (median, 16 days; p < 0.01) with low-dose Cyclosporin A (1.5 mg/kg bw). In pharmacokinetic experiments, the corneal radioactivity 24 h after intraperitoneal injection of 125I-labeled ART-18 was < 1% (p < 0.01) of the values obtained by subconjunctival injection, whereas the serum radioactivity values (p > 0.05) were in the same range. The above results suggest that the onset of an allograft reaction in perforating keratoplasty seems to depend on the locally achievable antibody concentration and can be delayed with a high level of IL-2 R mab present in the immediate surrounding of the foreign antigen-expressing cells.

[Ab-interno sclerostomy with the excimer laser via a quartz fiber in albino rabbits]. / Ab-interno Sklerostomie mit dem Excimerlaser über Quarzfaser am Albinokaninchen.

After attempting to induce experimental glaucoma in 20 albino rabbits by topical administration of 0.1% dexamethasone, ab-interno sclerostomy with an excimer laser at 308 nm via a quartz fiber was performed in one eye of each animal. Preoperatively, the sclera was stained with a UV-absorbing drug (sulfisomidine) in 10 rabbits; to shield the lens from scattered radiation, another UV absorber (fluorescein) was injected additionally into the anterior chamber. The other 10 rabbits were operated on without pretreatment. A full-thickness sclerostomy was performed in all animals. Most of the eyes upon operated showed minimal inflammation in the first few postoperative days. The intraocular pressure in the operated eyes was reduced compared to the fellow eye for about 3 months. Histology showed a 50-microns broad, smooth, thermally damaged zone at the edges of the sclerostomy. Clinical and histological investigation showed no evidence of UV-induced damage on the lens or retina in either group. Application of the UV absorber led to a significant decrease in the number of pulses required to perforate the sclera, but had no influence on the clinical history.