Progress in the study of diabetic retinopathy

Lei Xiao,Jun-Guo Duan

1Chengdu University of Traditional Chinese Medicine,Chengdu,China.

Abstract Diabetic retinopathy(DR)is one of the microvascular complications of diabetes,which could be divided into non-proliferative DR and proliferative DR according to the severity of retinopathy.Diabetic microangiopathy not only affects the eyesight of patients with diabetes,but also endangers the lives of patients.Therefore,DR has drawn more and more attention from domestic and foreign scholars.The etiology and treatment of diabetes are reviewed to explore ways of treating diabetic retinopathy.

Key words:Diabetic retinopathy,Pathogenesis,Treatment

Pathogenesis

The pathological process of diabetic retinopathy(DR)is mainly manifested as microvascular tumor formation,retinal vessels and small artery occlusion,new blood vessels and fibrous tissue hyperplasia and retinaldetachment.The fundusshowed retinal capillary hemangioma,bleeding spots,hard exudates and cotton wool spots,macular edema or ischemia,hemorrhage and vitreous body.The mechanisms for DR were complex[1],including abnormal polyol pathway,the accumulation of advanced glycation end products, oxidative stress, interleukin-1 (IL-1)abnormal level etc.

Abnormal polyol pathway

In high glucose condition,polyolpathway is hyperactivity.Research showed that[2]when the level of blood glucose elevated,glucose could be metabolized not only through glycolysis,but also through the polyol pathway.In the polyol pathway,glucose is converted into sorbitol,then sorbitol is converted to fructose under the action of sorbitol dehydrogenase.Sorbitol and fructose in the cell increased the cell osmotic pressure,which can cause cell swelling and structural damage.It is often manifested as the formation of retinal microangioma in the eyes[3].In addition,the production of polyol could reduce the antioxidant capacity and accelerate the apoptosis of retinal endothelial cells,which leads to the emergence of DR.

The accumulation of advanced glycation end products

The final product is a kind of compound formed by the non-enzymatic reaction of the amino group of the carbonyl group and the protein or lipids.Related animal experiment found that,the end product of glycosylation has increased the level of adhesion factor in the cell,which can affect the function of blood-retina barrier[4].Patients with long-term high blood sugar levels have a high rate of accumulation of advanced glycation end products that lead to the development of DR by activating a variety of detrimental signaling pathways.

Oxidative stress

Oxidative stress refers to the imbalance between the level of reactive oxygen species in the body and the endogenous antioxidant system.Under the condition of high blood glucose concentration,the electron transport chain in mitochondria is enhanced,which leads to the prolongation of the half-life of the superoxide intermediate productand enhanced oxidative stress[5].

IL-1

DR patients are impaired in vascular endothelial cells,resulting in increased plasma IL-1.The related research showed that the level of plasma IL-1 in diabetic patients had correlation with microangiopathy.The symbols in the eyes include a strong contraction of retinal vascular endothelial cells,which will cause retinal focal hypoperfusion and cause ischemia and hypoxia in the retina,further induce endothelial cells,pigment epithelial cells,and peripheral cells to produce too much VEGF,so as to enhance the permeability of blood vessels.This shows that abnormal IL-1 level is an important factor leading to DR.

Modern medicine treatment

Based on the control of blood glucose and blood lipids and other basic treatments,the appropriate eye treatment should be selected according to the severity of the patient's lesion.

Basic treatment

A large number of research data show that the blood pressure,blood glucose,blood lipid metabolism abnormalities may aggravate retinal microcirculation in diabetes.Hypertension can not only cause vascular disease,but also cause serious microvascular lesions(retinopathy,glomerular lesions,peripheral vascular disease etc).High blood sugar can cause metabolic disorder of the patients,leading to the occurrence and development of DR.High cholesterol can lead to endothelialdysfunction,excessive expression of inflammatory factors,which lead to DR.Therefore,reducing blood sugar and blood pressure and blood lipid levelcould improve microcirculation and protect the retinal function.Therefore,good control of blood pressure,blood glucose and blood lipids is an important prerequisite for the prevention and treatment of DR.

Pancreatic kininogenase

Kallikrein kinin system activation in vivo,improve the kinin level and inhibit mesangial proliferation and reduce the production and release of vascular endothelial.This further could lead to the expansion of blood vessels, improve microcirculation,effectively and prevent the formation of diabetic retinal microvascular tumor.Pancreatic kininogenase improves vascular permeability by acting directly on the small blood vessels and capillaries by increasing kinin levels.This shows that pancreatic kallikrein,as a microcirculation improving agent,is efficacy and mild,which is suitable for all kinds of early DR and a variety of diseases caused by diabetes microvascular circulation.

In addition, for patients with severe non-proliferative and proliferative DR,anti-VEGF treatment combined with surgical treatment are good choice.

Chinese medicine treatment

DR was not recorded in traditional Chinese medicine(TCM),but the symptoms have been recorded in many books of TCM.According to the different visual material changes, it is classified as"ophthalmology"and"violent blindness"in TCM ophthalmology.Some scholars have also proposed that the disease should be classified as"diabetes eye disease"according to the origin of the disease.

Syndrome differentiation

Clinically,there are differentopinions on the syndrome differentiation of DR.In TCM treatment,remedial drugs should focus on the nature syndrome and be administered according to the different syndromes.The common clinicaltypes are Qi and Yin deficiency,Yin and Yang deficiency,liver-kidney Yin deficiency,blood stasis syndrome.A large number ofclinicaltrials showed thatcorrect syndrome differentiation is effective for the treatment of DR.Gao H et al.[7]treated 32patients based on Xuanfu theory,according to TCM syndrome,patients with Yin-deficiency and blood-heat were treated with Nourishing Yin and Cold Blood Soup;patients with Qi-Yin deficiency were treated with nourishing Qi Soup,patients with liver depression and spleen deficiency type were treated with liver decompression and moistening Soup.The research shows that,after treatment,patient's symptoms and signs were effectively improved.Kinwell et al.[8]treated patients with Qi and Yin damage with Buyanghuanwu Soup, treatedpatients with liver-kidney Yin deficiency with Qijudihuang Soup,treated patients with deficient spleen with Senlingbaizhu powder and treated patients with blood stasis with Xuefuzhuoyu Soup,accompanied with blood circulation the collateralgoods.The research shows that, after treatment, patient's symptoms and signs were effectively improved.Wang J et al.[9]treated patients with Liuweidihuang Soup as the basic prescription based on the symbol of Yin-deficiency.Prescription for patients with yin deficiency and fire hyperactivity were added with Huangbai (Cortex phellodendri) and Zhimu(Rhizoma Anemarrhenae).Prescription for patients with Qi Yin deficiency were added with Maidong(Winterfell) and Taizishen (Crown prince).Prescription for patients with spleen and kidney deficiency were added with Huangqi(Astragalus),baizhu(White Atractylodes Rhizome)and Dangshen(Codonopsis pilosula).The research shows that,after treatment,patient's symptoms and signs were effectively improved.

Prescription

The prognosis of patients with DR was complicated and affected by congenital,individualphysical symptomsand individualdifferences.Treatment based on syndrome differentiation could improve the therapeutic effect.Li et al[10]compared the effects of Da Ming Yin and Calcium Dobesilate and found that Da Ming Yin had advantage over Calcium Dobesilate.Da Ming Yin was conducted by Sun He and concluded Huangqi(Astragalus),Shudihuang(Rehmannia),Yuzhu (Polygonatum),chuanqiong(Rhizoma Chuanxiong),Chaihu(Radix Bupleuri).Theherbsofnourishing Yin and Qiin this prescription can improve the circulation,so that alleviate the local symptoms.Liu et al[11]came up with a nourishing Yin and cold blood Soup based on the"Xuanfu stagnation"theory.By soothing liver-Qi stagnation,the symptoms were relieved.

Chinese herbal extracts

With the wide researches,the efficacy of herbal extracts is supported by more evidences.It shows that puerarin has the pharmacological action of antioxidation[12].Yue et al[13]study suggests puerarin has certain protective effect of diabetic retinal tissue through inhibiting the activation of protein kinase C in retinal tissue,and reducing the activity of vascular endothelialgrowth factor expression. Huangqi polysaccharide also has antioxidant effects.Si et al[14]found that Huangqi(Astragalus)polysaccharides may be one of the effective components of Huangqi. Huangqi polysaccharides can protect hydrogen peroxide-induced oxidative damage of RGC-5 cells,and the anti-oxidative effect of Huangqi(Astragalus)polysaccharides may have a protective effect on retinal ganglion cell damage in diseases such as DR.Emodin can inhibit the proliferation of vascular smooth muscle cells,and with the high blood glucose concentration,the inhibition of the proliferation of retinal vascular endothelial cells are similar.Therefore,it is effective for the treatment of DR.

Chinese patent medicine

Chinese patent medicine is widely applied.Ma et al[15]treated DR patients with Xuesaitong Capsule.The amplitude of the retinal oscillatory potential,retinal hemodynamic characteristics were studied and analyzed and results showed that Xuesaitong Capsule has a certain effect.Xu et al[16]treated patients with Xuesaitong Capsule oralcombined with compound anisodine injection treatment of DR,the results show that Xueshuantong Capsule combined with compound anisodine injection can improve the fundus microcirculation repair vascular lesions.

Combined use of acupuncture and medicine

A large numberofstudies[17]showed that acupuncture therapy has a dredging effect on the fundus blood vessels of DR.On the basis of local acupoints,the meridian theory is used to assist with the remote acupoints,which has the effect of reducing the meridians and the Yin and Yang.Therefore,more and more attentions have been paid to the clinical treatment of DR.Zhang et al[18]treated 16 DR patients with Da Ming Yin combined with electro-acupuncture.Thesetreatmentcould repair the spleen and kidney.The results showed the treatment were effective.

Combined treatment of TCM and Western medicine

TCM with western medicine in the treatment of DR can inhibit the progression of disease,improve the clinical efficacy.Zhang et al[20]showed that calcium dobesilate plus TCM therapy could improve the non-proliferative DR(NPDR)small infarction,capillary occlusion,hypoxic-ischemicsymptoms.Yuan et al[21]combined Shenqimaixintong Capsule with western medicine and found that the combination ofTCM and Western medicine treatment of neovascular was significant and safe.Chen et al [22] combined retinal laser photocoagulation after treatment of severe NPDR of DR,the results showed that the combination of TCM and Western medicine is safe and effective.

Discussion

With the continuous advance of diabetes,diabetic microvascular diseases have emerged,such as DR,which seriously affects the visual acuity and the quality oflife.Therefore,early detection and diagnosis can obtain satisfactory treatment effect.DR is a treatment clinical problem at present.There is no specific treatment.Under the control of the primary disease,TCM combined with Western medicine treatment can early prevent DR and improve visual acuity and quality of life.It is expected to become a new method for treatment of DR.

To sum up,for patients with early nonproliferative DR,drug treatments are good choose.For patients with severe nonproliferative and proliferative DR,drug treatment combined with surgical treatment are best choose,and the combination of TCM and Western medicine is also a good choose.