Diabetic Lens Research Articles

Astragalin attenuates diabetic cataracts via inhibiting aldose reductase activity in rats.

To investigate the aldose reductase (AR) inhibition capacity of astragalin (AST) against streptozoticin-induced diabetic cataracts (DCs) in rats. Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor (AAH) of pH 7.8 at room temperature with cataract-causing substance (55 mmol/L of galactose) and in vivo studies were performed on rats via induction with streptozotocin. AST was administered at different dose levels and scrutinize for DC activity. In diabetic rats, AST improved the body weight, blood insulin, and glucose as well as the levels of galactitol in a dose-dependent way, other biochemical parameters i.e. inflammatory mediators and cytokines, and also suppress AR activity. The level of the antioxidant parameters such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activity were also altered on a diabetic lens after the administration of the AST. AST protects against lens opacification to avoid cataracts and polyols formation, indicating that it could be used as a potential therapeutic agent for diabetes.

Aquaporins contribute to vacuoles formation in Nile grass type II diabetic rats.

Regulation of ion and water microcirculation within the lens is tightly controlled through aquaporin channels and connexin junctions. However, cataracts can occur when the lens becomes cloudy. Various factors can induce cataracts, including diabetes which is a well-known cause. The most common phenotype of diabetic cataracts is a cortical and/or posterior subcapsular opacity. In addition to the three main types and two subtypes of cataracts, a vacuole formation is frequently observed; however, their origin remains unclear. In this study, we focused on the aquaporins and connexins involved in diabetes-induced cataracts and vacuoles in Nile grass type II diabetes. The results showed that the expression of aquaporin 0 and aquaporin 5 increased, and that of connexin 43 decreased in diabetic rat lenses. Additionally, aquaporin 0 and 5 were strongly localized in peripheral of vacuoles, suggesting that aquaporins are involved in vacuoles formation. Transillumination photography revealed large vacuoles at the tip of the Y-suture in the anterior capsule of the diabetic lens, and several small vacuoles were observed in the posterior capsule. Within the vacuoles, cytoplasmic degradation and aggregation of fibrous material were observed. Our findings suggest that aquaporins are potential candidate proteins for preventing vacuole formation.

Dielectric response to thermal denaturation of lenses in healthy and diabetic rabbits

The relative permittivity and conductivity of healthy and alloxane-induced diabetic rabbits lenses were measured over a frequency range of 500 Hz to 100 kHz in an electric field and at temperatures from 25 to 150 °C. The dielectric spectra for both tissues showed two separate relaxations with a characteristic frequency of around 4 and 25 kHz assigned to the cortical and nuclear zones, respectively. These two dispersions are due to the interfacial polarization at the surface of the α-crystallin molecules. The denaturation temperature for the non-diabetic lens and the diabetic lens is approximately 70 and 80 °C, respectively. Moreover, the relative permittivity and conductivity values are higher in the diabetic lens than in the non-diabetic tissue at the same temperature and frequency. Our dielectric studies provide a better understanding of the thermal stability of crystallin-water complexes in normal and diseased human lenses.

Advanced glycation end products in human diabetic lens capsules

Advanced glycation end products (AGEs) accumulate with age in human lens capsules. AGEs in lens capsules potentiate the transforming growth factor beta-2-mediated mesenchymal transition of lens epithelial cells, which suggests that they play a role in posterior capsule opacification after cataract surgery. We measured AGEs by liquid chromatography-mass spectrometry in capsulorhexis specimens obtained during cataract surgery from nondiabetic and diabetic patients with and without established retinopathy. Our data showed that the levels of most AGEs (12 out of 13 measured) were unaltered in diabetic patients and diabetic patients with retinopathy compared to nondiabetic patients. There was one exception: glucosepane, which was significantly higher in diabetic patients, both with (6.85 pmol/μmol OH-proline) and without retinopathy (8.32 pmol/μmol OH-proline), than in nondiabetic patients (4.01 pmol/μmol OH-proline). Our study provides an explanation for the similar incidence of posterior capsule opacification between nondiabetic and diabetic cataract patients observed in several studies.

MicroRNA-199a-5p regulates epithelial-to-mesenchymal transition in diabetic cataract by targeting SP1 gene

BackgroundAs a common ocular complication of diabetes mellitus, diabetic cataract is becoming a leading cause of visual impairment. The progression of diabetic cataract progression involves epithelial-to-mesenchymal transition (EMT), the precise role of which remains to be investigated. As microRNAs (miRNAs) are suggested to be involved in the pathogenesis of many diseases, identification of aberrantly expressed miRNAs in diabetic lens epithelial cells (LECs) and their targets may provide insights into our understanding of diabetic cataract and potential therapeutic targets.MethodsDiabetic cataract capsules and LECs exposed to high glucose (25 mmol/L, 1–5 days) were used to mimic the model. Quantitative RT-PCR was performed to evaluate the differential expression of miRNA. Dual luciferase reporter assay was used to identify the binding target of miR-199a-5p. The expression of EMT-associated proteins was determined by immunofluorescence and Western blot analysis.ResultsOur results showed the differential expression of miR-9, -16, -22, -199a and -204. MiR-199a was downregulated in diabetic cataract capsule and hyperglycemia-conditioned human LECs. Specific protein 1 could be directly targeted and regulated by miR-199a in LECs and inhibit EMT in diabetic LECs.ConclusionOur findings implied miR-199a could be a therapeutic target by regulating SP1 directly to affect EMT in diabetic cataract and provided novel insights into the pathogenesis of diabetic cataract.

Mapping glucose metabolites in the normal bovine lens: Evaluation and optimisation of a matrix-assisted laser desorption/ionisation imaging mass spectrometry method.

The spatial resolution of microdissection-based analytical methods to detect ocular lens glucose uptake, transport and metabolism are poor, whereas the multiplexing capability of fluorescence microscopy-based approaches to simultaneously detect multiple glucose metabolites is limited in comparison with mass spectrometry-based methods. To better understand lens glucose transport and metabolism, a more highly spatially resolved technique that maintains the fragile ocular lens tissue is required. In this study, a sample preparation method for matrix-assisted laser desorption/ionisation imaging mass spectrometry (MALDI IMS) analysis of ocular lens glucose uptake and metabolism has been evaluated and optimised. Matrix choice, tissue preparation and normalisation strategy were determined using negative ion mode MALDI-Fourier transform-ion cyclotron resonance MS of bovine lens tissue and validation performed using gas chromatography-MS. An internal standard was applied concurrently with N-(1-naphthyl)ethylenediamine dihydrochloride (NEDC) matrix to limit cracking of the fresh frozen lens tissue sections. MALDI IMS data were collected at a variety of spatial resolutions to detect both endogenous lens metabolites and stable isotopically labelled glucose introduced by ex vivo lens culture. Using this approach, initial steps in important metabolic processes that are linked to diabetic cataract formation were spatially mapped in the bovine lens. In the future, this method can be applied to study the dynamics of glucose uptake, transport and metabolic flux to aid in the study of diabetic lens cataract pathophysiology.

Klotho ameliorates the onset and progression of cataract via suppressing oxidative stress and inflammation in the lens in streptozotocin-induced diabetic rats

Increased oxidative stress and inflammation play an important role in the pathogenesis of diabetic cataract. Klotho, known as an anti-ageing protein, has antioxidative and anti-inflammatory properties. Klotho is expressed in limited tissues including the lens. Here we examined whether klotho expression is decreased in diabetic lens and, if so, whether klotho treatment can prevent diabetic cataract formation. Streptozotocin (STZ)-induced diabetic rats and age-matched control rats were treated with vehicle or klotho protein, starting at 1 week after STZ injection. Twelve weeks after treatment, cataract formation was observed in diabetic rats but not control rats. Cataract formation and scores were significantly less in klotho-treated diabetic rats than vehicle-treated diabetic rats. Levels of klotho in plasma, aqueous humor and lens were significantly decreased in vehicle-treated diabetic rats, compared with control rats, but were restored in klotho-treated diabetic rats. Additionally, vehicle-treated diabetic rats had increased oxidative stress and inflammation in the lens, which were associated with decreased antioxidant transcriptional master regulator Nrf2 activity and increased transcription factor NF-κB activity. All of these findings were ameliorated in klotho-treated diabetic rats. Notably, klotho treatment did not alter blood glucose in diabetic rats. These results indicate that klotho reduction may increase susceptibility of the lens to oxidative and inflammatory insults, promoting cataract formation under diabetic conditions. Klotho treatment can ameliorate the onset and progression of diabetic cataract via enhancing Nrf2-mediated antioxidant defense and suppressing NF-κB-mediated inflammatory responses. Klotho in the lens may be a novel therapeutic target for prevention of cataract formation in diabetes.

Involvement of Oxidation and Glycation in Protein Modification in Diabetic Rat Lens

Involvement of Oxidation and Glycation in Protein Modification in Diabetic Rat Lens

Preventive Effects of Aphanothece sacrum on Diabetic Cataracts

Approximately 20% of diabetic patients develop diabetic cataracts. As lens proteins are known to be only slightly metabolized during the lifetime, cataracts are difficult to recover from once they have progressed. Therefore, the daily intake of natural compounds would be an important strategy for the prevention of diabetic cataracts. Aphanothece sacrum Okada (Asa) is a freshwater blue-green algae endemic to Japan. It has been eaten since the Edo period in Kyushu. In this study, the inhibitory effects of Asa on the pathogenesis of diabetic cataracts were evaluated. Furthermore, the inhibitory effects of Asa on the formation of Nε-(carboxymethyl) lysine (CML), an oxidation-dependent advanced glycation end-product, were also measured. After 3-month administration, the CML contents in the lens were measured by liquid chromatography tandem mass spectrometry using an internal standard of CML or lysine. Asa significantly inhibited the progression of cataractogenesis and accumulation of CML in diabetic lens compared with the normal diet group. These results suggested that daily intake of Asa reduces oxidative stress and prevents the pathogenesis of cataracts.

Anti-cataract Effect of Resveratrol in High-Glucose-Treated Streptozotocin-Induced Diabetic Rats.

Resveratrol, which is a polyphenol found in grapes, peanuts, and other plants, has health benefits for various chronic diseases. The aim of the present study was to examine the effect of resveratrol on cataract formation in diabetic rats. Male Wistar rats (7-week-old) were treated with streptozotocin, and the streptozotocin-treated animals were administered 5% D-glucose in drinking water to promote the formation of cataracts by inducing severe hyperglycemia. Resveratrol supplementation (10 or 30 mg/kg/d) in drinking water was initiated immediately after induction of diabetes was confirmed. The full lens images of the horizontal plane were captured with the digital camera system which we developed. Cataract formation was assessed by an observer-based scoring method and by quantitative analysis of digital images of the lens. Cataracts at the peripheral region of the lens were detected 2 weeks after induction of hyperglycemia and progressed depending on the length of the diabetic period. The majority of them developed severe cataracts after 9 weeks of hyperglycemia. Resveratrol did not prevent the appearance of diabetic cataracts but significantly delayed the progression of cataracts compared with controls. The contents of sorbitol and protein carbonyls in lenses of diabetic rats were higher than those of control rats. Resveratrol suppressed the increase in protein carbonyls, but not of sorbitol, in diabetic lenses. These results suggest that resveratrol delays the progression of diabetic cataracts partially through attenuation of oxidative damage to lens proteins. Resveratrol may be beneficial in preventing the progression of diabetic cataracts.

The expression change of autophagy-related factors in lens epithelial cells of diabetic mice

Objective To investigate the role of autophagy in the development of diabetic cataract by detecting the expression of autophagy-related factors (BECN1, LC3B, P62) in diabetic mouse lens epithelial cells. Methods Eighty C57BL/6 male mice were selected.Fifty C57 mice were consecutively dosed with streptozotocin (STZ) 50 mg/(kg·d) by intraperitoneal injection to induce type 1 diabetes mellitus model, and served as the model group; the remaining 30 mice were injected with appropriate dose of citrate buffer, and served as the control group.The fasting plasma glucose was tested by collecting the caudal vein blood in the model group.The morphological changes of autophagy of lens epithelial cells were observed by transmission electron microscopy.The expression and localization of LC3B and P62 protein were detected by immunohistochemistry.PCR was used to detect the expression of BECN1, LC3B and P62 mRNA in the anterior capsule.The relative expression of autophagy-related proteins in the anterior capsule was detected by Western blot.The use of animals complied with Regulations on the Management of Experimental Ainimals from Shandong Eye Institute. Results Compared with the control group, transmission electron microscopy revealed that the autophagosomes of lens epithelial cells in model group was large and contained more mitochondria.Immunohistochemical method showed that the expression of LC3B and P62 proteins in the anterior capsule tissue of experiment group was stronger than that of the control group.The relative expression level of BECN1, LC3B and P62 mRNA in the experiment group was 1.48±0.10, 2.62±0.15 and 1.89±0.20, respectively, which was higher than 1.10±0.02, 1.10±0.05 and 1.01±0.01 in the control group, with significant differences between the two groups (t=6.64, 14.25, 6.14; all at P<0.05). The relative expression of BECN1, LC3B and P62 protein in the experiment group was 1.50±0.10, 1.24±0.09 and 3.19±1.04, respectively, which was higher than 1.00±0.00, 1.00±0.00 and 1.00±0.00 in the control group, with significant differences between the two groups (t=8.75, 6.10, 3.65; all at P<0.05). Conclusions The phenomenon of autophagy in lens epithelial cells of diabetic mice is abnormal, and autophagy dysfunction may play an important role in the formation of diabetic cataract. Key words: Diabetic cataract; Autophagy; Lens epithelial cells; BECN1; LC3B; P62

The modulation of the phosphorylation status of NKCC1 in organ cultured bovine lenses: Implications for the regulation of fiber cell and overall lens volume

In previous work, we have shown the Sodium/Potassium/2 Chloride Cotransporter (NKCC1) to be a key effector of lens fiber cell volume regulation. Since others have shown that the activity of NKCC1 is regulated via its phosphorylation status, the purpose of this study was to investigate whether NKCC1 phosphorylation can be modulated in organ cultured bovine lenses, and to see how this relates to changes in lens wet weight. Western blotting was first used to confirm the expression of NKCC1, phosphorylated NKCC1 (NKCC1-P) and the regulatory kinases WNK/SPAK and phosphatases PP1/PP2A in bovine lenses at the protein level. Changes to NKCC1-P status were then assessed by organ culturing bovine lenses in either isotonic, hypertonic or hypotonic solutions in the presence or absence of the NKCC inhibitor, bumetanide, or phosphatase inhibitors okadaic acid and calyculin A. After 1–22 h of culturing, lenses were weighed, assessed for transparency and the cortical protein fractions analyzed by western blot using antibodies to detect total NKCC1 and NKCC1-P. NKCC1, NKCC1-P, SPAK, PP1 and PP2A were all detected in the membrane fraction of bovine lenses. Under hypertonic conditions, NKCC1 is phosphorylated and activated to mediate a regulatory volume increase. Finally, NKCC1-P signal increased in the presence of phosphatase inhibitors indicating that PP1/PP2A can dephosphorylate NKCC1. These results show that the phosphorylation status and hence activity of NKCC1 is dynamically regulated and that in response to hypertonic stress, NKCC1 activity is increased to effect a regulatory volume increase that limits cell shrinkage. These findings support the view that the lens dynamically regulates ion fluxes to maintain steady state lens volume, and suggest that dysfunction of this regulation maybe an initiating factor in the localized fiber cell swelling that is a characteristic of diabetic lens cataract.

Aphanothece sacrum (Sur.) Okada Prevents Cataractogenesis in Type 1 Diabetic Mice.

Aphanothece sacrum (Sur.) Okada is a species of cyanobacteria found in Japan. Although it has been used in local cuisine in Kyushu, Japan, for 250 y, little is known about its beneficial effect as food. The daily intake of health beneficial phytochemicals is believed to be useful for preventing lifestyle-related diseases, such as diabetic cataracts. In this study, the inhibitory effect of freeze-dried A. sacrum (Asa) on the formation of diabetic cataracts (DCs) was evaluated. Type 1 diabetes was induced in mice using streptozotocin (STZ). The mice were divided into two groups: one was fed a normal diet (DM-control group) and the other was fed a diet containing 1% Asa (DM-Asa group). During the study, changes in blood glucose levels and the amount of food and water consumed were measured. After 3 mo, the amount of Nε-(carboxymethyl)lysine (CML), an oxidative stress marker, in the lens was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the blood glucose levels (p=0.91) and food consumption did not significantly change in any group, the oral administration of Asa tended to suppress CML accumulation (p=0.15) and significantly inhibited the progression of cataractogenesis in the diabetic lens compared with that reported for the normal diet (p=0.009). These results suggested that the daily intake of A. sacrum prevents the pathogenesis of cataracts, and indicated that may reduce the number of DC patients.

Melatonin reduces lens oxidative stress level in STZ-induced diabetic rats through supporting glutathione peroxidase and reduced glutathione values

Hyperglycemia plays a critical role in the development and progression of diabetic cataract oxidative injuries via the increased reactive oxygen species (ROS) production. Melatonin has been considered a potent strong antioxidant that detoxifies a variety of ROS in many metabolic diseases. The present study was conducted to explore whether melatonin administration protects against diabetic lens oxidative injuries through modulation of reduced glutathione (GSH) and glutathione peroxidase (GPx) systems in streptozotocin (STZ)-induced diabetic rats. Thirty two rats were equally divided into four groups as control, STZ, melatonin and STZ and melatonin. The third and fourth groups received intraperitoneal 10 mg/kg melatonin for 2 weeks. For induction of diabetes in the second and fourth groups, intraperitoneal STZ (45 mg/kg) was given. Lipid peroxidation (MDA), total oxidant status and intracellular ROS levels in the lens were increased in STZ group although they were decreased by melatonin treatment. GPx activity, GSH concentration and total antioxidant status (TAS) were lower in STZ group than in control. However, the GSH concentration, GPx activity and TAS levels were recovered by melatonin. TAS was also higher in melatonin group than in the STZ and melatonin groups. In conclusion, the present study shows that melatonin induced protective effects against diabetes-induced lens oxidative injury through up-regulation of the GSH and GPx values but down-regulation of oxidative stress.

Fundus autofluorescence lifetimes are increased in non-proliferative diabetic retinopathy.

To discriminate non-proliferative diabetic retinopathy (NPDR) patients from healthy controls by fluorescence lifetime imaging ophthalmoscopy (FLIO). A prototype FLIO (Heidelberg-Engineering, Heidelberg, Germany) was used to examine the retina of 33 patients and 28 controls. As increased fluorescence of the diabetic lens is known, the lenses of 34 patients and 24 controls were investigated as well. Time-resolved decay was detected in two spectral channels (ch1: 498-560nm, ch2: 560-720nm) and approximated by a series of three exponential functions yielding in lifetimes (τ1 , τ2 , τ3 ), amplitudes (α1 , α2 , α3 ) and their amplitude-weighted means (τm ). Significant differences between patients and controls were found for all fundus lifetime components (τm , τ1 -τ3 ) as for the amplitude α3 in both spectral channels. Channel 1 showed the largest differences: the average of mean fluorescence lifetime τm in the macula was 259±137ps in the patients versus 147±69ps in the controls. A logistic regression model allowed discrimination between study and control group with a sensitivity of 90.09% and a specificity of 71.4% (area under the curve: 0.865). Significantly shorter τm in the patients group than in the control group was detected in channel 2 in the crystalline lens (1587±326ps versus 1854±384ps, p=0.006). Fundus Fluorescence lifetimes are significantly increased in NPDR while lens lifetimes are shorter in the patient group. Lifetime changes might be indicative for the accumulation of advanced glycation end products (AGEs) which enables detection of the disease with high sensitivity and specificity possibly bearing diagnostic merit.

Metabolism and detoxification of the lipid derived aldehyde, 4-Hydroxynonenal in diabetic cataractogenesis in rat

To study the metabolism of 4-hydroxynonenal (HNE), one of lipid derived aldehydes (LDAs), in diabetic rat lens and its role in diabetic cataract formation. Experimental research. A factor design was used to set up the experiment statistically upon two factors: diabetic and normal control as treatment factors; day 30, 45 and 70 as the time factors. Normal and diabetic rats' lenses were incubated with HNE for 2 hours. HNE metabolites in the culture media were studied by high performance liquid chromatography (HPLC). Aldehyde dehydrogenase (ALDH) activity in normal and diabetic rat lens (30, 45 and 70 d after inducing of cataract) was detected by a spectrophotometer, ALDH protein and HNE-protein were detected by Western Blot. All data were analyzed by the Bonferroni test using SAS 8.0 software. The major pathway for HNE metabolism in normal lens was conjugation with glutathione (GSH) to form GS-HNE (45%), followed by HNE's oxidation to 4-hydroxy-2-nonenoic acid (HNA) by ALDH, which accounted for approximately 9.1% of HNE. The conjugation of HNE with GSH in diabetic lens was decreased approximately 64% at day 30 compared with the controls (F = 49.59, P < 0.001). The pathway of HNE oxidation by ALDH in the diabetic lens was enhanced approximately 1.7 times at day 70 compared to day 30 (F = 11.51, P = 0.0442). A higher ALDH activity, greater amount of ALDH protein, and less amount of HNE-protein adduct were presented in diabetic rat lens. The pathway of conjugation of HNE with GSH is inhibited in diabetic lens which may play a role in the formation of diabetic cataract. The oxidation of HNE by ALDH is a compensation process for protecting the lens against diabetic damage.

Numerical modeling of refractive changes in diabetic subjects

T aim of the study was to reconstruct the optical conditions inside the diabetic crystalline lens. Optical parameters of the crystalline lens were affected by homeostasis disorders associated with diabetes. The changes of optical parameters in subjects with diabetes are usually described with statistical methods (1) and the results of these statistical analyses rarely provide clear and unequivocal results. In the case of parameters that require high sensitivity measurements, the results often turn out to be located at the borderline of statistical significance. Thus, in such cases it is necessary to use more stable and predictable equivalents of these structures. For numerical simulations, a model of crystalline lens was constructed. The model was based on geometric parameters (2), physiological data (3) with gradient index (GRIN) of optical medium of the lens (4). The GRIN was modified according to our knowledge about changes of crystalline lens in diabetic patient (1). We examined refractive power and spherical aberration and their changes for possible disturbances. The present study has shown that the changes of gradient profile have the influence on the optical power of the lens and the value of spherical aberration as well. Furthermore, the study has proved the possible reduction of changes of optical parameters of the lens due to swelling by GRIN. When the lens swells, the focal length becomes shortened and spherical aberration is bigger. The results from simulation are clear because the mathematical model proves the relationship between the geometry of the lens and GRIN and image reproduction.

Effect of chronic hyperglycemia on crystallin levels in rat lens

Crystallins are the major structural proteins in the vertebrate eye lens that contribute to lens transparency. Although cataract, including diabetic cataract, is thought to be a result of the accumulation of crystallins with various modifications, the effect of hyperglycemia on status of crystallin levels has not been investigated. This study evaluated the effect of chronic hyperglycemia on crystallin levels in diabetic cataractous rat lens. Diabetes was induced in rats by injecting streptozotocin and maintained on hyperglycemia for a period of 10weeks. At the end, levels of α-, β-, γ-crystallins and phosphoforms of αB-crystallins (αBC) were analyzed by immunoblotting. Further, solubility of crystallins and phosphoforms of αBC was analyzed by detergent soluble assay. Chronic diabetes significantly decreased the protein levels of α-, β- and αA-crystallins (αAC) in both soluble and insoluble fraction of lens. Whereas γ-crystallin levels were decreased and αBC levels were increased in lens soluble fraction with no change in insoluble fraction in diabetic rat lens. Although, diabetes activated the p38MAPK signaling cascade by increasing the p-p38MAPK in lens, the phosphoforms of αBC were decreased in soluble fraction with a concomitant increase in insoluble fraction of diabetic lens when compared to the controls. Moreover, diabetes strongly enhances the degradation of crystallinsand phosphoforms of αBC in lens. Taken together, the decreased levels of crystallins and insolubilization of phosphoforms of αBC under chronic hyperglycemia could be one of the underlying factors in the development of diabetic cataract.

Effects of long-acting somatostatin analogues on redox systems in rat lens in experimental diabetes

The effects of long-acting somatostatin analogues, angiopeptin (AGP) and Sandostatin (SMS), on the early decline in the lens content of glutathione (GSH), ATP and NADPH and increase in sorbitol were studied in STZ diabetic rats, and comparison was made with the effect of insulin. Three factors prompted this study: (i) the known increase in IGF-1 in ocular tissue in diabetes and antagonistic effect of somatostatins, (ii) the known effect of IGF-1 in increasing lens aldose reductase and (iii) the lack of effect of somatostatins on diabetic hyperglycaemia, the latter enabling a differentiation to be made between effects of hyperglycaemia per se and site(s) of IGF-1/somatostatins. All four metabolites studied showed a significant restoration towards the normal control level after 7days of treatment with AGP and SMS, and AGP was more effective on levels of GSH and ATP. A significant correlation was found between GSH and ATP across all groups at 7days treatment. The redox state changes in diabetes include both NADP+/NADPH and NAD+/NADH in the conversion of glucose to sorbitol and via sorbitol dehydrogenase to fructose with a linked decrease in ATP formation via NAD+/NADH regulation of the glycolytic pathway. The interlinked network of change includes the requirement for ATP in the synthesis of GSH. The present study points to possible loci of action of somatostatins in improving metabolic parameters in the diabetic rat lens via effects on aldose reductase and/or glucose transport at GLUT 3.

Observation on the ultrastructure of cataract lens epithelial cells

Objective To study the relationship of cataract with lens epithelial cell apoptosis and autophagy by observing the ultrastructure of age-related and diabetic cataract lens epithelial cells.Methods Transmission electron microscope was used to observe the apoptotic and autophagic morphology of the lens epithelial cells in 5 cases with age-related and diabetic cataract respectively,and in 2 cases with normal lens.Results The apoptosis and autophagy of lens epithelial cells was found in cases with age-related and diabetic cataract,while no expression was observed in control lens epithelial cells.Conclusion The apoptosis and autophagy of lens epithelial cells are closely related to age-related and diabetic cataract formation. Key words: Cataract; Lens epithelial cells; Apoptosis; Autophagy