Recent Advances and Disputes About Curcumin in Retinal Diseases

Abstract

Curcumin belongs to the group of so-called phytocompounds, biologically active molecules produced by plants exerting a beneficial effect on health. Curcumin shows a wide spectrum of different properties, being an anti-inflammatory, antioxidant, antimicrobial and antimutagenic molecule. The purpose of the review is to examine what literature reported on the characteristics of curcumin, particularly, on the beneficial and controversial aspects of this molecule, aiming for a better therapeutic management of retinal diseases. The retina is a constant target of oxidative stress, this tissue being characterized by cells rich in mitochondria and by vessels and being, obviously, continuously reached from photons affecting its layers. Particularly, the retinal ganglion cells and the photoreceptors are extremely sensitive to oxidative stress damage and it is well known that an imbalance in reactive oxygen species is often involved in several retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, central serous chorioretinopathy, macular edema, retinal ischemia-reperfusion injury, proliferative vitreoretinopathy, hereditary tapeto-retinal degenerations, and retinal and choroidal tumors. To date, several studies suggest that oral treatment with curcumin is generally well tolerated in humans and, in addition, it seems to have no negative effects: therefore, curcumin is a promising candidate as a retinal disease therapy. Unfortunately, the primary limitation of curcumin is represented by its poor bioavailability, in fact only a minimal fraction of this substance can reach the blood stream in the form of a biologically active compound. However, many steps have been made in several fields. In the future, it is expected that the strategies developed until now to allow curcumin to reach the target tissues in adequate concentrations could be ameliorated and, above all, large in vivo studies on humans are needed to demonstrate the total safety of these compounds and their effectiveness in different eye diseases.

Keywords: anti-inflammatory proprieties; antioxidant proprieties; exosomes; miRNA; nanosphere; natural compounds.

Figure 1

Chemical structure of the curcumin.

Scheme 1

Pathways for ocular disease and biochemical properties of curcumin. Proliferation pathway: CDK4, cyclin D1, c-myc; cell survival pathway: Bcl-2, Bcl-xL; caspase activation pathway: caspase 8/3/9; molecular pathways containing the protein kinase c-Jun N-terminal kinases: JNK; protein kinase B: PKB; reactive oxygen species: ROS; endothelial vascular cell adhesion molecule-1: VCAM-1; intracellular adhesion molecule-1: ICAM-1; leukocyte adhesion molecule-1: ELAM-1; metalloproteinases: MMP; serine protease family: SP; urokinase plasminogen activator system: uPA; tumor suppressor pathway: p53, p21; death receptor pathway: DR4, DR5; cyclooxygenase-2: COX-2; 5-lipoxygenase: 5-LOX; prostaglandin E2: PGE2; nuclear factor –κB: NF-κB; activator protein-1: AP-1; xanthine oxidase: XO; janus kinase, signal transducer and activator of transcription: JAK/STAT; tumor necrosis factor-α: TNF-α; proinflammatory interleukins: IL-1, IL-2, IL-6, IL-8 and IL-12; peroxisome proliferator-activated receptor-γ: PPAR-γ; vascular endothelial growth factor: VEGF; transforming growth factor: TGF-β1; stimulate the fibroblasts expression of fibronectin: FN; collagen.

Figure 2

Spectral domain-optical coherence tomography of a right eye affected by age-related macular degeneration (AMD). Macular neuroepthelial detachment (central thickness of 419 µm) and choroidal neovascular membrane (CNV).

Figure 3

Spectral domain-optical coherence tomography of a right eye affected by diabetic macular edema (ME). Spongy aspect of neuroretin (central thickness of 520 µm) and hyperreflectivity of epiretinal membrane.

Figure 4

Retinal angiography of a right eye affected by recurrent central serous chorioretinopathy (CSC).

Figure 5

Retinal angiography of a left eye affected by Irvine Gass syndrome. Macular and parapapillary (temporal edge) edema after cataract surgery in a patient suffering from chronic glaucoma with excavated and pale optic disc.

Figure 6

Panels of retinal angiography in central venous thrombosis with ischemic-edema and chorioretinal laser treatment.

Figure 7

Spectral domain-optical coherence tomography in left eye of retinitis pigmentosa patient. It is possible to observe: an epiretinal membrane between the optic disc and the macula; loss of the photoreceptor layer beyond the fovea; increase of the central nuclear layer.