SUMMARY The mechanisms causing the steady-state force enhancement following active skeletal muscle stretching are not well understood. Recently, we found direct evidence that part of the force enhancement is associated with the engagement of a passive component. In this study, we reproduced the conditions that give consistent passive force enhancement and evaluated the mechanical properties of this passive force enhancement so as to gain insight into its source. The three primary results were that (1) the passive force enhancement is long lasting (>25 s), (2) passive force enhancement was reduced in a dose-dependent manner by the amount of shortening preceding active muscle stretching, and (3) passive force enhancement could be abolished`instantaneously' by shortening-stretching the passive muscle by an amount equivalent to the active stretch magnitude. Together with the remaining results, we conclude that the source of the passive force enhancement must be arranged in parallel with the contractile force, it must consist of a viscoelastic molecular spring whose stiffness characteristic can be reset by shortening, and it must have a characteristic length that is governed by the length of the contractile components, possibly the sarcomeres. Based on these results, the molecular spring titin emerges as a possible candidate for the passive component of the steady-state force enhancement observed in this and previous studies.

Aim: To measure corneal and scleral radii of curvature in response to intraocular pressure (IOP). Methods: Using digital photographic profile images of 16 fresh porcine eyes, the curvatures of the cornea and sclera were determined in response to five consecutive incremental 100 ml saline intravitreal injections. IOP was measured and ocular rigidity calculated. Elastic moduli of the cornea and sclera were estimated. Results: Intraocular pressure and the radius of curvature of the sclera increased linearly with increasing volume. There was no statistical change in corneal curvature. The elasticity of the cornea and sclera was constant during the 15-50 mm Hg increase in IOP. The estimated range of the elastic moduli of the cornea and sclera were, respectively 0.07-0.29 MPa and 0.2 MPa to 0.5 MPa. The scleral rigidity ranged from 0.0017 to 0.0022. Conclusions: The elastic moduli of the cornea and sclera are independent of IOP. The modulus of elasticity of the sclera is higher than that of the cornea. Elevation of IOP changes the curvature of the sclera but not that of the cornea. Porcine scleral rigidity is similar to human scleral rigidity. Scleral curvature could be a novel method for measuring IOP. F riedenwald 1 was the first to define scleral rigidity in terms of ocular volume and intraocular pressure (IOP). He realised that the sclera was important in understanding the effects of IOP on the optic nerve, and that the manifestations of glaucoma and the severity of its sequelae may be dependent on scleral rigidity. Recently, a non-linear finite element sensitivity study demonstrated that the stiffness of the sclera was the most important factor for determining the vulnerability of the optic nerve head to increasing IOP.2 This study demonstrated that even large strains of neural tissue had less effect on the optic nerve head than the indirect effects of IOP on the sclera. The effect of increasing IOP on scleral deformation has not been quantified. As the eyeball is a biological and a curved structure, a sensitive method is required to measure the small deformational changes induced by fluctuations in IOP. This study investigates the change in radii of curvatures of the fresh intact porcine cornea and sclera with IOP. Ocular rigidity is calculated and the ranges of elastic moduli of the cornea and sclera are estimated. METHODSSixteen porcine eyes were obtained from the local abattoir; eyes were collected was within 4 h of death and then transported on ice. All eyes were from animals aged 5.5 months. Experiments were completed between 3-6 h postmortem. During the preparation and experiment, samples were kept moist with saline solution. The extraocular muscles and extraneous fat were carefully removed from each eyeball and each specimen weighed on a digital balance before and after experimentation.At 20˚C, the eyeballs were placed, with their optic axes horizontal, on a specially designed base made of hollow, clear perspex tubing with gradation along the edge, to enable them to be maintained in a secure position duri...

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There are no treatments for reversing or halting cataract, a disease of the structural proteins in the eye lens, that has associations with other age-related degenerative conditions such as Alzheimer's disease. The incidence of cataract and associated conditions is increasing as the average age of the population rises. Protein folding diseases are difficult to assess in vivo as proteins and their age-related changes are assessed after extraction. Nanotechnology can be used to investigate protein changes in the intact lens as well as for a potential means of drug delivery. Nanoparticles, such as cerium oxide (CeO(2)) which have antioxidant properties, may even be used as a means of treating cataract directly. Prior to use in treatments, nanoparticle genotoxicity must be tested to assess the extent of any DNA or chromosomal damage. Sister chromatid exchanges were measured and DNA damage investigated using the alkaline COMET assay on cultured human lens epithelial cells, exposed to 5 and 10 microg ml(-1) of CeO(2) nanoparticles (nanoceria). Nanoceria at these dosages did not cause any DNA damage or significant increases in the number of sister chromatid exchanges. The absence of genotoxic effects on lens cells suggests that nanoceria, in the doses and exposures tested in this study, are not deleterious to the eye lens and have the potential for use in studying structural alterations, in developing non-surgical cataract treatments and in investigating other protein folding diseases.

PF-04523655 showed a dose-related tendency for improvement in BCVA in DME patients. Studies of higher doses are planned to determine the optimal efficacious dose of PF-04523655. PF-04523655 may offer a new mode of therapeutic action in the management of DME. (ClinicalTrials.gov number, NCT00701181.).

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Taprenepag isopropyl significantly reduces IOP in POAG and ocular hypertension. Taprenepag isopropyl monotherapy is comparable to latanoprost 0.005% in reducing IOP. As demonstrated in this report, the activity of taprenepag isopropyl is additive to that of latanoprost 0.005%. Further studies are required to determine whether it shows similar additivity when administered with other ocular antihypertensive medications.