Our study has provided evidence that DIBI has anti-inflammatory effects in experimental uveitis. Additionally, no local ocular toxicity was observed.

Interstitial cystitis (IC) is a chronic bladder disorder with unclear etiology. The endocannabinoid system has been identified as a key regulator of immune function, with experimental evidence for the involvement of cannabinoid receptors in bladder inflammation. This study used intravital microscopy (IVM) and behavioral testing in lipopolysaccharide-induced IC, to investigate the anti-inflammatory analgesic effects of a natural dietary sesquiterpenoid, beta-caryophyllene (BCP), which is present in cannabis among other plants, and has reported agonist actions at the cannabinoid 2 receptor (CB2R). BCP’s anti-inflammatory actions were compared to the synthetic CB2R-selective cannabinoid, HU308, and to an FDA-approved clinical treatment (dimethyl sulfoxide: DMSO). IVM data revealed that intravesical instillation of BCP and/or HU308 significantly reduces the number of adhering leukocytes in submucosal bladder venules and improves bladder capillary perfusion. The effects of BCP were found to be comparable to that of the selective CB2R synthetic cannabinoid, HU308, and superior to intravesical DMSO treatment. Oral treatment with BCP was also able to reduce bladder inflammation and significantly reduced mechanical allodynia in experimental IC. Based on our findings, we believe that CB2R activation may represent a viable therapeutic target for IC, and that drugs that activate CB2R, such as the generally regarded as safe (GRAS) dietary sesquiterpenoid, BCP, may serve as an adjunct and/or alternative treatment option for alleviating symptoms of inflammation and pain in the management of IC.

The ocular microcirculation represents an important target to treat inflammatory diseases of eye, where impairment of microvascular blood flow plays key role as, for example, in anterior uveitis. To evaluate novel interventions targeting the microcirculation, appropriate and reliable tools to study this particular microvascular bed are needed. Intravital microscopy (IVM) belongs to several methods allowing evaluation of microcirculation experimentally, even in small animals. The aim of our study was to examine the iridial microcirculation (IMIC) in uveitis induced by local or systemic endotoxin administration in rats and mice by IVM and to propose new parameters to quantify the changes within the IMIC. Systemic inflammation was induced in rats by intravenous endotoxin administration, control group received normal saline intravenously. Local inflammation was induced in mice by intravitreal endotoxin administration, the control group received normal saline intravitreally. IVM of IMIC was performed in animals receiving systemic endotoxin prior injection and 1 and 2 h afterwards, respectively, in animals receiving intravitreal endotoxin/saline prior local injection and 5 h afterwards. Obtained video recordings were analyzed off-line. Functional capillary density (FCD) and dysfunctional capillary density (DCD) were evaluated for description of IMIC, and calculation of FCD/DCD ratio was performed. In systemic inflammation, FCD was significantly decreased compared to control animals. In local inflammation, the number of functional capillaries in the IMIC was significantly reduced following the endotoxin challenge. Analysis of the DCD revealed a significant increase in capillaries with reduced perfusion after intravitreal endotoxin administration and right shift of the FCD/DCD ratio was observed after endotoxin local injection. Detecting and quantifying changes in IMIC during systemic or local inflammation in experimental animals by IVM was feasible. Therefore, IVM of the IMIC represents a valuable tool to evaluate and quantify inflammatory changes in experimental eye disease.