Development of an Algorithm to Indicate the Right Moment of Plant Watering Using the Analysis of Plant Biomasses Based on Dahlia × hybrida

Water management in agriculture and horticulture has a strong ecological importance related to the necessity of optimizing the use of water resources. To achieve sustainable water use, it is necessary to optimize the time, frequency and the methods of water application. In this study, we hypothesized that the right moment for watering may be established on the grounds of the observation of the physiological state of the plant (if the plant is still in turgor) and the biomass of plant and the substrate. The proper irrigation scheduling, that is, just before the plant loses turgor, which appears at ca. 73% of LRWC in dahlias, determined with the use of the proposed measurement and computing system, makes it possible to save ca. 30% of irrigation water, in comparison to standard watering. Controlled watering also affected plant growth parameters, such as the content of chlorophyll a and b and carotenoid, as well as total and reducing sugar content (ca. 7%, 9% and 23% more than in plants watered in a standard way, respectively). Plants watered in a controlled way were 12% more compact when compared with the ones watered in a standard way. The results clearly proved that the computing system connected to scales made it possible to save water used for irrigation without a negative impact on the parameters of plant growth

Decreased Circulation in the Feline Choriocapillaris Underlying Retinal Photocoagulation Lesions

Panretinal photocoagulation is used to treat diabetic retinopathy. Measurements with SLO and microspheres show that the choriocapillaris is locally damaged under lesions in the cat retina. This damage could limit the effectiveness of photocoagulation

Safety and Biodistribution Evaluation in Cynomolgus Macaques of rAAV2tYF-CB-hRS1, a Recombinant Adeno-Associated Virus Vector Expressing Retinoschisin

viii, 164 hlm; 14x21 c

Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity.

Increased exposure to blue or visible light, fluctuations in oxygen tension, and the excessive accumulation of toxic retinoid byproducts places a tremendous amount of stress on the retina. Reduction of visual chromophore biosynthesis may be an effective method to reduce the impact of these stressors and preserve retinal integrity. A class of non-retinoid, small molecule compounds that target key proteins of the visual cycle have been developed. The first candidate in this class of compounds, referred to as visual cycle modulators, is emixustat hydrochloride (emixustat). Here, we describe the effects of emixustat, an inhibitor of the visual cycle isomerase (RPE65), on visual cycle function and preservation of retinal integrity in animal models. Emixustat potently inhibited isomerase activity in vitro (IC50 = 4.4 nM) and was found to reduce the production of visual chromophore (11-cis retinal) in wild-type mice following a single oral dose (ED50 = 0.18 mg/kg). Measure of drug effect on the retina by electroretinography revealed a dose-dependent slowing of rod photoreceptor recovery (ED50 = 0.21 mg/kg) that was consistent with the pattern of visual chromophore reduction. In albino mice, emixustat was shown to be effective in preventing photoreceptor cell death caused by intense light exposure. Pre-treatment with a single dose of emixustat (0.3 mg/kg) provided a ~50% protective effect against light-induced photoreceptor cell loss, while higher doses (1-3 mg/kg) were nearly 100% effective. In Abca4-/- mice, an animal model of excessive lipofuscin and retinoid toxin (A2E) accumulation, chronic (3 month) emixustat treatment markedly reduced lipofuscin autofluorescence and reduced A2E levels by ~60% (ED50 = 0.47 mg/kg). Finally, in the retinopathy of prematurity rodent model, treatment with emixustat during the period of ischemia and reperfusion injury produced a ~30% reduction in retinal neovascularization (ED50 = 0.46mg/kg). These data demonstrate the ability of emixustat to modulate visual cycle activity and reduce pathology associated with various biochemical and environmental stressors in animal models. Other attributes of emixustat, such as oral bioavailability and target specificity make it an attractive candidate for clinical development in the treatment of retinal disease

Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity.

Increased exposure to blue or visible light, fluctuations in oxygen tension, and the excessive accumulation of toxic retinoid byproducts places a tremendous amount of stress on the retina. Reduction of visual chromophore biosynthesis may be an effective method to reduce the impact of these stressors and preserve retinal integrity. A class of non-retinoid, small molecule compounds that target key proteins of the visual cycle have been developed. The first candidate in this class of compounds, referred to as visual cycle modulators, is emixustat hydrochloride (emixustat). Here, we describe the effects of emixustat, an inhibitor of the visual cycle isomerase (RPE65), on visual cycle function and preservation of retinal integrity in animal models. Emixustat potently inhibited isomerase activity in vitro (IC50 = 4.4 nM) and was found to reduce the production of visual chromophore (11-cis retinal) in wild-type mice following a single oral dose (ED50 = 0.18 mg/kg). Measure of drug effect on the retina by electroretinography revealed a dose-dependent slowing of rod photoreceptor recovery (ED50 = 0.21 mg/kg) that was consistent with the pattern of visual chromophore reduction. In albino mice, emixustat was shown to be effective in preventing photoreceptor cell death caused by intense light exposure. Pre-treatment with a single dose of emixustat (0.3 mg/kg) provided a ~50% protective effect against light-induced photoreceptor cell loss, while higher doses (1-3 mg/kg) were nearly 100% effective. In Abca4-/- mice, an animal model of excessive lipofuscin and retinoid toxin (A2E) accumulation, chronic (3 month) emixustat treatment markedly reduced lipofuscin autofluorescence and reduced A2E levels by ~60% (ED50 = 0.47 mg/kg). Finally, in the retinopathy of prematurity rodent model, treatment with emixustat during the period of ischemia and reperfusion injury produced a ~30% reduction in retinal neovascularization (ED50 = 0.46mg/kg). These data demonstrate the ability of emixustat to modulate visual cycle activity and reduce pathology associated with various biochemical and environmental stressors in animal models. Other attributes of emixustat, such as oral bioavailability and target specificity make it an attractive candidate for clinical development in the treatment of retinal disease

Reduced Retinal Neovascularization.

<p>The effect of emixustat on retinal neovascularization was studied in the mouse OIR model. Seven day-old mouse pups were subjected to hyperoxia (75% oxygen) for 5 days. On P12, the mice were returned to room air and daily treatments with ruboxistaurin (10 mg/kg), emixustat (0.03–3.0 mg/kg), or appropriate vehicles were administered as described in <i>Methods</i>. Retinal flat mounts were prepared and areas of NV were quantified; these data were compared to data from control mice that were maintained in a normoxic environment (21% oxygen). Mice that were moved from a hyperoxic to normoxic environment, without treatment, showed a significant extent of retinal NV (~30% of the retinal area). Treatment with the ruboxistaurin (positive control) reduced the area of NV to ~20% of the total retinal area. In mice treated with emixustat, a dose-dependent reduction in retinal NV was observed. The reduction in NV at the highest emixustat dose (3.0 mg/kg/day) approached a level that was comparable to that obtained with ruboxistaurin (Fig 6A; *, t-test, p<0.05). The ED₅₀ for reduction of retinal NV in emixustat-treated mice was 0.46 mg/kg/day. Representative retinal flat mounts from an untreated, normoxic control, an untreated OIR control, and in a 3 mg/kg emixustat-treated mouse are shown in panels B, C, and D, respectively. Areas of NV, outlined in red tracings, were identified and quantified using Adobe Photoshop software.</p

Processing of Vitamin A in The Visual Cycle.

<p>Enzymatic processing within the visual cycle begins with delivery of vitamin A (all-<i>trans</i>-retinol) from the blood circulation. Upon entry into the RPE, all-<i>trans</i>-retinol is converted to a retinyl ester through the activity of lecithin retinol acyl transferase (1). The resulting all-<i>trans</i>-retinyl ester pool represents a storage form of vitamin A upon which RPE65 acts to generate 11-<i>cis</i>-retinol (2); 11-<i>cis</i>-retinol is then oxidized by an 11-<i>cis</i>-specific retinol dehydrogenase to form the visual chromophore, 11-<i>cis</i>-retinal (3). The visual chromophore is delivered to rod and cone outer segments (4) where it combines with opsins to form visual pigments (e.g., rhodopsin). Light activation of rhodopsin initiates visual transduction processes and liberates all-<i>trans</i>-retinal as a photoproduct. Reduction of all-<i>trans</i>-retinal, via all-<i>trans</i>-retinal dehydrogenase, produces all-<i>trans</i>-retinol (5), which is transferred back to the RPE for recycling. The continued activity of RPE65 in the light state ensures sustained levels of rhodopsin, closure of ion channels through transducin activation, and reduced oxygen demand.</p