Robust visual cortex evoked potentials (VEP) in Gnat1 and Gnat2 knockout mice.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin, imparting to themselves the ability to respond to light in the absence of input from rod or cone photoreceptors. Since their discovery ipRGCs have been found to play a significant role in non-image-forming aspects of vision, including circadian photoentrainment, neuroendocrine regulation, and pupillary control. In the past decade it has become increasingly clear that some ipRGCs also contribute directly to pattern-forming vision, the ability to discriminate shapes and objects.

Impaired Light Adaptation of ON-Sustained Ganglion Cells in Early Diabetes Is Attributable to Diminished Response to Dopamine D4 Receptor Activation.

Purpose: Retinal neuronal signaling is disrupted early in diabetes, before the onset of the vascular pathologies associated with diabetic retinopathy. There is also growing evidence that retinal dopamine, a neuromodulator that mediates light adaptation, is reduced in early diabetes. Previously, we have shown that after 6 weeks of diabetes, light adaptation is impaired in ON-sustained (ON-s) ganglion cells in the mouse retina.

Dopamine D1 and D4 receptors contribute to light adaptation in ON-sustained retinal ganglion cells.

The adaptation of ganglion cells to increasing light levels is a crucial property of the retina. The retina must respond to light intensities that vary by 10-12 orders of magnitude, but the dynamic range of ganglion cell responses covers only ∼3 orders of magnitude. Dopamine is a crucial neuromodulator for light adaptation and activates receptors in the D1 and D2 families.

Early diabetes impairs ON sustained ganglion cell light responses and adaptation without cell death or dopamine insensitivity.

Retinal signaling under dark-adapted conditions is perturbed during early diabetes. Additionally, dopamine, the main neuromodulator of retinal light adaptation, is diminished in diabetic retinas. However, it is not known if this dopamine deficiency changes how the retina responds to increased light or dopamine.

Dopamine D1 receptor activation reduces local inner retinal inhibition to light-adapted levels.

During adaptation from dim to bright environments, changes in retinal signaling are mediated, in part, by dopamine. Dopamine is released with light and can modulate retinal receptive fields, neuronal coupling, inhibitory receptors, and rod pathway inhibition. However, it is unclear how dopamine affects inner retinal inhibition to cone bipolar cells, which relay visual information from photoreceptors to ganglion cells and are important signal processing sites.

Dopamine D1 receptor activation contributes to light-adapted changes in retinal inhibition to rod bipolar cells.

Dopamine modulation of retinal signaling has been shown to be an important part of retinal adaptation to increased background light levels, but the role of dopamine modulation of retinal inhibition is not clear. We previously showed that light adaptation causes a large reduction in inhibition to rod bipolar cells, potentially to match the decrease in excitation after rod saturation. In this study, we determined how dopamine D1 receptors in the inner retina contribute to this modulation.

Stromal vascular stem cell treatment decreases muscle fibrosis following chronic rotator cuff tear.

Purpose: Rotator cuff injuries are associated with atrophy and fat infiltration into the muscle, commonly referred to as "fatty degeneration." As the poor function of chronically torn muscles may limit recovery after surgical repair, there is considerable interest in finding therapies to enhance muscle regeneration. Stromal vascular fraction stem cells (SVFCs) can improve muscle regeneration in other chronic injury states, and our objective was to evaluate the ability of SVFCs to reduce fibrosis and fat accumulation, and enhance muscle fibre specific force production after chronic rotator cuff tear.

Changes in skeletal muscle and tendon structure and function following genetic inactivation of myostatin in rats.

Myostatin is a negative regulator of skeletal muscle and tendon mass. Myostatin deficiency has been well studied in mice, but limited data are available on how myostatin regulates the structure and function of muscles and tendons of larger animals. We hypothesized that, in comparison to wild-type (MSTN(+/+) ) rats, rats in which zinc finger nucleases were used to genetically inactivate myostatin (MSTN(Δ/Δ) ) would exhibit an increase in muscle mass and total force production, a reduction in specific force, an accumulation of type II fibres and a decrease and stiffening of connective tissue.

Inhibition of 5-LOX, COX-1, and COX-2 increases tendon healing and reduces muscle fibrosis and lipid accumulation after rotator cuff repair.

Background: The repair and restoration of function after chronic rotator cuff tears are often complicated by muscle atrophy, fibrosis, and fatty degeneration of the diseased muscle. The inflammatory response has been implicated in the development of fatty degeneration after cuff injuries. Licofelone is a novel anti-inflammatory drug that inhibits 5-lipoxygenase (5-LOX), as well as cyclooxygenase (COX)-1 and COX-2 enzymes, which play important roles in inducing inflammation after injuries.

Aging-associated exacerbation in fatty degeneration and infiltration after rotator cuff tear.

Background: Rotator cuff tears are one of the most common musculoskeletal complaints and a substantial source of morbidity in elderly patients. Chronic cuff tears are associated with muscle atrophy and an infiltration of fat to the area, a condition known as "fatty degeneration." To improve the treatment of cuff tears in elderly patients, a greater understanding of the changes in the contractile properties of muscle fibers and the molecular regulation of fatty degeneration is essential.

Targeted inhibition of TGF-β results in an initial improvement but long-term deficit in force production after contraction-induced skeletal muscle injury.

Transforming growth factor-β (TGF-β) is a proinflammatory cytokine that regulates the response of many tissues following injury. Previous studies in our lab have shown that treating muscles with TGF-β results in a dramatic accumulation of type I collagen, substantial fiber atrophy, and a marked decrease in force production. Because TGF-β promotes atrophy and fibrosis, our objective was to investigate whether the inhibition of TGF-β after injury would enhance the recovery of muscle following injury.