Ágnes Berta

Localization of caveolin-1 and c-src in mature and differentiating photoreceptors: raft proteins co-distribute with rhodopsin during development.

Numerous biochemical and morphological studies have provided insight into the distribution pattern of caveolin-1 and the presence of membrane rafts in the vertebrate retina. To date however, studies have not addressed the localization profile of raft specific proteins during development. Therefore the purpose of our studies was to follow the localization pattern of caveolin-1, phospho-caveolin-1 and c-src in the developing retina and compare it to that observed in adults. Specific antibodies were used to visualize the distribution of caveolin-1, c-src, a kinase phosphorylating caveolin-1, and phospho-caveolin-1. The labeling pattern of this scaffolded complex was compared to those of rhodopsin and rhodopsin kinase. Samples were analyzed at various time points during postnatal development and compared to adult retinas. The immunocytochemical studies were complemented with immunoblots and immunoprecipitation studies. In the mature retina caveolin-1 and c-src localized mainly to the cell body and IS of photoreceptors, with only very weakly labeled OS. In contrast, phospho-caveolin-1 was only detectable in the OS of photoreceptors. During development we followed the expression and distribution profile of these proteins in a temporal sequence with special attention to the period when OS formation is most robust. Double labeling immunocytochemistry and immunoprecipitation showed rhodopsin to colocalize and co-immunoprecipitate with caveolin-1 and c-src. Individual punctate structures between the outer limiting membrane and the outer plexiform layer were seen at P10 to be labeled by both rhodopsin and caveolin-1 as well as by rhodopsin and c-src, respectively. These studies suggest that membrane raft specific proteins are co-distributed during development, thereby pointing to a role for such complexes in OS formation. In addition, the presence of small punctate structures containing caveolin-1, c-src and rhodopsin raise the possibility that these proteins may transport together to OS during development and that caveolin-1 exists predominantly in a phosphorylated form in the OS.

Intraarticular Injection of a Cross-Linked Sodium Hyaluronate Combined with Triamcinolone Hexacetonide (Cingal) to Provide Symptomatic Relief of Osteoarthritis of the Knee: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Trial

Objective: To evaluate the efficacy and safety of an intraarticular injection of Cingal (Anika Therapeutics, Inc., Bedford, MA) compared with Monovisc (Anika Therapeutics, Inc., Bedford, MA) or saline for the treatment of knee osteoarthritis. Design: This multicenter, double-blind, saline-controlled clinical trial randomized subjects with knee osteoarthritis (Kellgren-Lawrence grades I-III) to a single injection of Cingal (4 mL, 88 mg hyaluronic acid [HA] plus 18 mg triamcinolone hexacetonide [TH]), Monovisc (4 mL, 88 mg HA), or saline (4 mL, 0.9%). The primary efficacy outcome was change in WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain Score through 12 weeks with Cingal versus saline. Secondary outcomes included Patient and Evaluator Global Assessments, OMERACT-OARSI Responder index, and WOMAC Total, Stiffness, and Physical Function scores through 26 weeks. Results: A total of 368 patients were treated (Cingal, n = 149; Monovisc, n = 150; saline, n = 69). Cingal improvement from baseline was significantly greater than saline through 12 weeks (P = 0.0099) and 26 weeks (P = 0.0072). WOMAC Pain was reduced by 70% at 12 weeks and by 72% at 26 weeks with Cingal. Significant improvements were found in most secondary endpoints for pain and function at most time points through 26 weeks. At 1 and 3 weeks, Cingal was significantly better than Monovisc for most endpoints; Cingal and Monovisc were similar from 6 weeks through 26 weeks. A low incidence of related adverse events was reported. Conclusions: Cingal provides immediate and long-term relief of osteoarthritis-related pain, stiffness, and function, significant through 26 weeks compared to saline. Cingal had similar immediate advantages compared with HA alone, while showing benefit comparable to HA at 6 weeks and beyond.

Surgical Techniques in Cartilage Repair Surgery: Osteochondral Autograft Transfer (OATS, Mosaicplasty)

Various surgical methods exist for the treatment of focal chondral and osteochondral defects of weight-bearing articular surfaces. Traditional resurfacing techniques provide reparative fibrocartilage coverage of the lesion with poor biomechanical properties and suboptimal clinical outcome. Recent advances in treatment options including osteochondral allografts aim to provide hyaline or hyaline-like repair for articular defects. Although previous publications on autogenous osteochondral transplantation reported long-term hyaline cartilage survival on the transplanted osteochondral block [3, 6, 23, 26], clinical use of single-block osteochondral transfer had been restricted by limited donor-site availability. Also, use of large grafts can cause incongruity at the recipient site, which permanently alters the biomechanics of the joint [5, 7, 9–12]. Our preclinical animal studies performed between 1991 and 1992 showed that the use of small-sized multiple cylindrical grafts, rather than a single large block graft, allows more tissue to be transplanted while preserving donor-site integrity and the mosaic-like implanting fashion permits progressive contouring of the new surface [13, 15].

Distribution of caveolin isoforms in the lemur retina

The distribution of caveolin isoforms was previously evaluated in the retinas of different species, but has not yet been described in the primate retina. In this study, the distribution of caveolins was assessed via immunochemistry using isoform-specific antibodies in the retina of the black-and-white ruffed lemur. Here, we report the presence of a variety of caveolin isoforms in many layers of the lemur retina. As normal human retinas were not available for research and the retinas of primates are fairly similar to those of humans, the lemur retina can be utilized as a model for caveolin distribution in normal humans.

Mosaicplasty of Osteochondral Lesions of the Ankle

The presence of cartilaginous bodies in the ankle joint was first reported by Monro in 1856 [1]. Term and nature of osteochondritis dissecans (OCD) were described in classic reports of Konig and Rendu [2, 3]. Davidson et al., Flick and Gould and Nash and Baker have all discussed the late finding of OCD lesions after an initially diagnosed “sprained ankle” [4–6]. Canale and Bending further emphasised trauma as a causative factor [7]. Lateral lesions cause more symptoms than medial OCDs. Also, lateral lesions have a higher incidence of a previous traumatic event. The head of the talus represents a less frequent location of talar OCD lesions, although recently, this location has also been described [8].

Mosaicplasty for Treatment of Osteochondral Defects of the Ankle

An osteochondral ankle defect is a lesion involving talar articular cartilage and subchondral bone and mostly caused by a single or multiple traumatic events, leading to partial or complete detachment of the osteochondral fragment with or without osteonecrosis (Zengerink et al., Knee Surg Sports Traumatol Arthrosc 18:942, 2009). One treatment possibility is mosaicplasty, which aims to replace the damaged hyaline cartilage and the underlying bone. Indication of mosaicplasty is usually secondary, because it is a relatively aggressive surgical procedure requiring the harvesting of a donor autologous osteochondral graft from a healthy knee joint, and for medial side defects, a malleolar osteotomy is often required. The mosaicplasty technique was reported by Hangody et al. in 1997 (Hangody et al., Foot Ankle Int 18(10):628–634, 1997). It involves transferring multiple cylindrical osteochondral grafts from the less weight-bearing area of the knee to the defect on the weight-bearing surface of the talus. The surgery is performed through a mini-arthrotomy, combined with a medial malleolar osteotomy if the lesion is located on the medial talar dome. Since the grafts superimpose onto each other, mosaicplasty allows for 90–95 % coverage of the defect. Analysis of clinical scores has shown good to excellent results in 93 % of talar mosaicplasties. However, complications have occurred including slight or severe degenerative changes at the recipient and/or donor sites, deep infections, and painful hemarthroses.

Rehabilitation After Replacement Procedures (i.e., OATS, Allograft)

Autologous osteochondral transplantation techniques, such as osteochondral autologous transfer system (OATS) and mosaicplasty, and osteochondral allograft transplantation aim to repair osteochondral lesions of the talus by providing a hyaline or a hyaline-like gliding surface over the affected area.