Net Charge and Nonpolar Content Guide the Identification of Folded and Prion Proteins.

The degree of hydrophobicity and net charge per residue are physical properties that enable the discrimination of folded from intrinsically disordered proteins (IDPs) solely on the basis of amino acid sequence. Here, we improve upon the existing classification of proteins and IDPs based on the parameters mentioned above by adopting the scale of nonpolar content of Rose et al. and by taking amino acid side-chain acidity and basicity into account. The resulting algorithm, denoted here as net charge nonpolar or NECNOP, enables the facile prediction of the folded and disordered status of proteins under physiologically relevant conditions with >95% accuracy, based on amino-acid sequence alone. The NECNOP approach displays a much-enhanced performance for proteins with >140 residues, suggesting that small proteins are more likely to have irregular charge and hydrophobicity features. NECNOP analysis of the entire Escherichia coli proteome identifies specific net charge and nonpolar regions peculiar to soluble, integral membrane, and non-integral membrane proteins. Surprisingly, protein net charge and hydrophobicity are found to converge to specific values as chain length increases, across the E. coli proteome. In addition, NECNOP plots enable the straightforward identification of protein sequences corresponding to prion proteins and promise to serve as a powerful predictive tool for the design of large proteins. In summary, NECNOP plots are a straightforward approach that improves our understanding of the relation between the amino acid sequence and three-dimensional structure of proteins as a function of molecular mass.

Full-thickness macular hole formation in eyes with a pre-existing complete posterior vitreous detachment.

BACKGROUND: Tangential macular traction by the posterior vitreous cortex has been widely accepted as the major causative factor in the development of idiopathic macular holes. Separation of the posterior cortical vitreous should relieve this vitreoretinal traction. METHODS: The authors report five patients with idiopathic full-thickness macular hole formation that occurred in the presence of a well-documented pre-existing complete posterior vitreous detachment. RESULTS: Of five eyes, three underwent pars plana vitrectomy and instillation of transforming growth factor-beta. No residual prefoveal cortical vitreous was present at the retinal surface at the time of surgery. Additionally, clinically identifiable epiretinal membranes were present in three of five eyes, but these epiretinal membranes were extremely thin, transparent, induced minimal traction, and did not warrant surgical peeling. CONCLUSION: It is likely that, in these five patients, some mechanism other than tangential traction by prefoveal vitreous cortex is responsible for idiopathic full-thickness macular hole formation.

Transforming growth factor-beta 2 levels increase following retinal laser photocoagulation.

To determine if the levels of transforming growth factor-beta 2 (TGF-beta 2) in ocular tissues change following laser photocoagulation, pigmented rabbit eyes underwent panretinal photocoagulation using laser indirect ophthalmoscopy. The rabbits were followed for a period of either 2 or 14 days after the procedure. The eyes were then removed and samples of vitreous and aqueous humor were collected. TGF-beta 2 levels were measured using an immunoassay. When compared to control eyes, TGF-beta 2 levels in the vitreous humor of treated eyes at day 2 and day 14 were increased. Changes in TGF-beta 2 levels were also seen in the aqueous humor of the treated eyes, with increased levels seen at day 2 and day 14 compared to control eyes. The increase in both vitreous and aqueous humor in treated eyes compared to control eyes was shown to be statistically significant (p < 0.05). Our results show that intraocular TGF-beta 2 levels increase significantly following laser photocoagulation. This preliminary study suggests that TGF-beta 2 may be involved in the process of chorioretinal wound healing.

The use of perfluoro-octane in the management of giant retinal tears without proliferative vitreoretinopathy.

PURPOSE: A technique for managing giant retinal tears without proliferative vitreoretinopathy (PVR) is presented, and visual outcome, anatomic reattachment, and postoperative complications are discussed. METHODS: A total of 25 consecutive cases of retinal detachment from giant retinal tears in eyes without PVR that had not previously undergone surgery were reviewed. A surgical technique combining pars plana vitrectomy, perfluoro-octane, and fluid-gas exchange was used. Scleral buckling was performed in 23 (92%) of 25 eyes, and pars plana lensectomy was performed in 11 (69%) of the 16 phakic eyes. A minimum follow-up period of 6 months was documented in each case. RESULTS: Of the 25 eyes, redetachment occurred in 3 (12%) after the initial procedure, and further surgery was necessary to successfully reattach the retina. A total of 9 secondary procedures were performed in 7 (28%) of the 25 eyes. Final retinal reattachment was achieved in all 25 eyes. Final Snellen visual acuity was 20/80 or better in 18 (72%) patients and 20/200 or better in 21 (84%) patients. CONCLUSION: The anatomic and visual results of this method of surgical treatment of giant retinal tears without PVR compare favorably to those achieved with techniques that use a nonbuckling approach, but with reduced ocular morbidity.

Indocyanine green angiography in multiple evanescent white-dot syndrome.

Using indocyanine green angiography we examined two patients with multiple evanescent white-dot syndrome. Both patients had unilateral loss of vision and a fundus appearance typical of multiple evanescent white-dot syndrome. Fluorescein angiography in both patients disclosed a patchy hyperfluorescent pattern at the level of the retinal pigment epithelium. Using indocyanine green angiography, we observed multiple deep, small, round hypofluorescent lesions that appeared early and persisted into the late phases. The spots appeared to block the underlying choroidal pattern. These hypofluorescent spots were clearly visible and present throughout the posterior pole. Many more spots were seen on indocyanine green angiography than were visible by clinical examination or angiography. After follow-up examinations, there was a rapid resolution of the spots over four to six weeks with return of vision. Our findings show that indocyanine green angiography can be a valuable tool in the recognition and further understanding of multiple evanescent white-dot syndrome.

Retreatment of full-thickness macular holes persisting after prior vitrectomy. A pilot study.

PURPOSE: Vitrectomy with fluid-gas exchange has been shown to close more than one half of full-thickness macular holes, with improvement in visual acuity. By adding the appropriate dose of transforming growth factor-beta 2, a higher success rate has been reported. However, there still remain cases of macular holes that fail to close after vitreous surgery. The current pilot study is designed to determine whether reoperation may have a role in the management of cases that fail after vitreous surgery. METHODS: Twelve eyes with persistent full-thickness macular holes that failed to close after an initial vitrectomy underwent reoperation using 1330 ng transforming growth factor-beta 2. RESULTS: After the second operation, closure occurred in 12 (100%) of 12 eyes. Follow-up ranged from 8 to 16 months. Visual acuity also improved by two or more lines in 5 (42%) of 12 patients. Increased nuclear sclerosis occurred in nine (90%) of the ten phakic eyes. Of the five eyes showing visual improvement, four required cataract extraction and intraocular lens implantation. CONCLUSION: Retreatment of persistent full-thickness macular holes with transforming growth factor-beta 2 appears to have a beneficial effect on both neurosensory retinal flattening and visual outcome.

Cataract formation following corneal transplantation in eyes with Fuchs' endothelial dystrophy.

In a retrospective analysis, 78 eyes in 58 patients that underwent corneal transplantation for Fuchs' endothelial dystrophy were examined for the presence of cataracts. Follow-up ranged from 1 to 17 years, with an average of 6.62 years. Thirty-four (44.1%) of the eyes developed cataracts sufficient enough to require surgical removal. The mean time from transplant to cataract formation averaged 4.9 years. The average age at the time of transplant surgery in the eyes that did not develop cataracts was 55.6, and in those that developed cataracts, 60.3 (p = 0.049). Thirteen percent of the transplants lost transparency following cataract extraction. The incidence of postkeratoplasty cataract increased at age 50 and occurred in 75% of eyes grafted in patients 60 years of age or older.