Anti-inflammatory Effect of Curcumin, Homotaurine, Vitamin D3 on Human Vitreous in Patients With Diabetic Retinopathy
Condition: Diabetic Retinopathy
MeSH terms: Retinal Diseases; Diabetic Retinopathy
Study type: Observational

Summary: 
      Dosage of pro-inflammatory cytokines and soluble mediators (TNFα, IL6, IL2 and PDGF-AB)
      performed on 25 vitreous biopsies taken from patients with diabetic retinopathy and treated
      with increasing doses of curcumin (0.5uM and 1uM), with or without homotaurine (100uM) and
      vitamin D3 (50nM).
    

Detailed description: 
      Diabetic retinopathy is one of the most common complications of diabetes mellitus and is a
      leading cause of vision loss and blindness in the working-age population worldwide. DR is
      being recognized as a neurodegenerative disease of the retina as opposed to previously
      considered solely as a microvascular disease. Progressive blindness is due to the long-term
      accumulation of pathological abnormalities in the retina of hyperglycemic patients. In the
      initial phase, non-proliferative diabetic retinopathy (NPDR) is almost asymptomatic with the
      onset of microhemorrhagic and microischemic episodes and an increase in vascular
      permeability. Subsequently, the progression of the disease is accompanied by the onset of a
      chronic inflammatory state and neovascularization in a vicious circle that feeds and
      determines the accumulation of damage to the retina through hypoxia, oxidative stress and
      widespread neurodegeneration. Among metabolites, hyperglycemia is known to be the major
      factor which activates several metabolic pathways harmful for retina. Moreover, an increased
      level of glutamate has been reported in the diabetic retina and also in the vitreous of
      diabetic patients, suggesting a neurotoxic role of glutamate which may damage retinal neurons
      and especially retinal ganglion cells by excitotoxicity. In proliferative diabetic
      retinopathy (PDR), vitreous humor undergoes structural and molecular changes, with changes
      also in composition, which play a central role in supporting disease progression.The
      vitreous, 4 ml in volume, is a transparent gel-like structure which fills the space between
      the lens and the retina. It is composed of 98-99% of water with traces of cations, ions,
      proteins (mainly collagen) and polysaccharides such as hyaluronic acid. In PDR patients
      undergoing pars plana vitrectomy, vitreous samples are characterized by altered levels of
      bioactive molecules with pro-angiogenic, proinflammatory and neuromodulatory activities. So,
      it is clear that the vitreous acts as a reservoir of soluble signaling mediators that could
      exacerbate retinal damage. On the other hand, the vitreous obtained from patients with PDR
      can be a powerful tool to evaluate the anti-angiogenic / anti-inflammatory activity of new
      biomolecules that could be potential candidates for the treatment of diabetic
      vitreoretinopathy. Currently, PDR is treated with laser photocoagulation, vitreoretinal
      surgery or intravitreal injection of drugs targeted to the vascular endothelial growth factor
      (VEGF) and steroid agents.However, these protocols are effective in the short term, cause
      side effects and, above all, are indicated only for advanced stages of the disease. So,
      noninvasive, nondestructive, and longer-duration treatment options are also needed. Recently,
      research eﬀorts have been made to identify neuroprotective drugs able to prevent visual ﬁeld
      loss and preserve visual function and a promising alternative for the treatment of
      early-stage NPDR comes from nutraceuticals. In fact, in vitro and in vivo studies have
      revealed that a variety of nutraceuticals has important antioxidant and anti-inflammatory
      properties that can compromise the first diabetes-driven molecular events that cause
      vitreoretinopathy, acting upstream of the disease. Based on the results of several
      investigations, it is reasonable to assert that a single constituent that aﬀects one target
      has limited eﬃcacy in preventing the progression of multifactorial diseases. A large body of
      research revealed that the use of a combination of compounds with synergistic multitarget
      eﬀects may oﬀer a more powerful approach for disease prevention, including retinal
      neurodegeneration. In experimental models of retinal neurodegeneration it has been shown that
      cotreatment of citicoline and homotaurine has a direct neuroprotective eﬀect on primary
      retinal cells exposed to glutamate toxicity and HG levels. Glutamate-induced excitotoxicity
      is implicated in the pathophysiology of several degenerative diseases of the retina,
      including glaucoma. Moreover, HG-induced neurotoxicity is a characteristic of diabetic
      retinopathy. Curcumin, a yellowish non-flavonoid polyphenol that constitutes the main active
      compound of Curcuma longa, is widely known for its antioxidant and anti-inflammatory
      properties . Many studies have also described its marked protective effect on retinal cells
      against oxidative stress and inflammation. Lastly, vitamin D levels appeared to be lower in
      diabetes mellitus type 2 patients and this could have therapeutic implications. Therefore,
      the aim of the investigator's study is to analyze the soluble mediators of inflammation and
      angiogenesis in the vitreous of patients with diabetic retinopathy treated with homotaurine,
      curcumin and vitamin D3.
    

Intervention name(s): curcumin, homotaurine, vitamin D3; control
Intervention type(s): Other; Other
Intervention description(s): ELISA tests on supernatants of 25 vitreous biopsies incubated with bioactive molecules at 37 ° C for 20 h. The concentration of soluble mediators was calculated from a calibration curve.; ELISA tests on supernatants of 25 vitreous biopsies. The concentration of soluble mediators was calculated from a calibration curve.
Intervention MeSH terms: Vitamin D; Cholecalciferol; Curcumin; Tramiprosate
Observational model: Other
Time perspective: Other
Sampling method: Non-Probability Sample
Study population: 
        25 patients aged ≥18 years with diabetic retinopathy requiring vitrectomy
      
Biospecimen description: 
      human vitreous
    
Keywords: neuroprotection; vitreous; pro-inflammatory cytokines; curcumin; vitamin D3; homotaurine