SignificanceDevelopment of treatments for hereditary degeneration of the retina (RD) is hampered by the vast genetic heterogeneity of this group of diseases and by the delivery of the drug to an organ protected by the blood–retina barrier. Here, we present an approach for the treatment of different types of RD, combining an innovative drug therapy with a liposomal system that facilitates drug delivery into the retina. Using different animal models of RD we show that this pharmacological treatment preserved both the viability of cells in the retina as well as retinal function. Thus, our study provides an avenue for the development of therapies for hereditary diseases which cause blindness, an unmet medical need.

Introduction: Flat foot (pes planus) is a commonly observed disorder in clinical practice. The height of Medial Longitudinal Arch (MLA) determines the degree of pes planus. Majority of the previous studies on prevalence of flexible flat foot were done among children.Aim: The present study was undertaken to determine the prevalence of flexible flat foot among 18-21-year-old Indian adults using Navicular Drop Test (NDT) which is regarded as reliable and valid method to characterise MLA.

Cone photoreceptor cell death as it occurs in certain hereditary retinal diseases is devastating, with the affected patients suffering from a loss of accurate and colour vision. Regrettably, these hereditary cone diseases are still untreatable to date. Thus, the identification of substances able to block or restrain cone cell death is of primary importance. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration (cpfl1). We show that HDAC inhibition protects cpfl1 cones in vitro, in retinal explant cultures. More importantly, in vivo, a single intravitreal TSA injection significantly increased cone survival for up to 16 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and retinal diseases associated with impaired cone migration.

Cone photoreceptors (cones) are essential for high-resolution daylight vision and colour perception. Loss of cones in hereditary retinal diseases has a dramatic impact on human vision. The mechanisms underlying cone death are poorly understood, and consequently, there are no treatments available. Previous studies suggest a central role for calcium (Ca) homeostasis deficits in photoreceptor degeneration; however, direct evidence for this is scarce and physiological measurements of Cain degenerating mammalian cones are lacking.Here, we took advantage of the transgenic HR2.1:TN-XL mouse line that expresses a genetically encoded Cabiosensor exclusively in cones. We cross-bred this line with mouse models for primary ("cone photoreceptor function loss-1", cpfl1) and secondary ("retinal degeneration-1", rd1) cone degeneration, respectively, and assessed resting Calevels and light-evoked Caresponses in cones using two-photon imaging. We found that Cadynamics were altered in cpfl1 cones, showing higher noise and variable Calevels, with significantly wider distribution than for wild-type and rd1 cones. Unexpectedly, up to 21% of cpfl1 cones still displayed light-evoked Caresponses, which were larger and slower than wild-type responses. In contrast, genetically intact rd1 cones were characterized by lower noise and complete lack of visual function.Our study demonstrates alterations in cone Cadynamics in both primary and secondary cone degeneration. Our results are consistent with the view that higher (fluctuating) cone Calevels are involved in photoreceptor cell death in primary (cpfl1) but not in secondary (rd1) cone degeneration. These findings may guide the future development of therapies targeting photoreceptor Cahomeostasis.

Retinal diseases caused by cone photoreceptor cell death are devastating as the patients are experiencing loss of accurate and color vision. Understanding the mechanisms of cone cell death and the identification of key players therein could provide new treatment options. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration (cpfl1). We show that HDAC inhibition protects cones in vitro, in retinal explant cultures. More importantly, in vivo a single TSA injection increased cone survival for up to 10 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and diseases associated with impaired cone migration.

Retinal cone photoreceptors (cones) serve daylight vision and are the basis of color discrimination. They are subject to degeneration, often leading to blindness in many retinal diseases. Calcium (Ca 2+ ), a key second messenger in photoreceptor signaling and metabolism, has been proposed to be indirectly linked with photoreceptor degeneration in various animal models. Systematically studying these aspects of cone physiology and pathophysiology has been hampered by the difficulties of electrically recording from these small cells, in particular in the mouse where the retina is dominated by rod photoreceptors. To circumvent this issue, we established a two-photon Ca 2+ imaging protocol using a transgenic mouse line that expresses the genetically encoded Ca 2+ biosensor TN-XL exclusively in cones and can be crossbred with mouse models for photoreceptor degeneration. The protocol described here involves preparing vertical sections ("slices") of retinas from mice and optical imaging of light stimulus-evoked changes in cone Ca 2+ level. The protocol also allows "in-slice measurement" of absolute Ca 2+ concentrations; as the recordings can be followed by calibration. This protocol enables studies into functional cone properties and is expected to contribute to the understanding of cone Ca 2+ signaling as well as the potential involvement of Ca 2+ in photoreceptor death and retinal degeneration.

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