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Lycium barbarum (wolfberry) reduces secondary degeneration and oxidative stress, and inhibits JNK pathway in retina after partial optic nerve transection.

Li H, Liang Y, Chiu K, Yuan Q, Lin B, Chang RC, So KF - PLoS ONE (2013)

Bottom Line: Our group has shown that the polysaccharides extracted from Lycium barbarum (LBP) are neuroprotective for retinal ganglion cells (RGCs) in different animal models.The expression of several proteins related to inflammation, oxidative stress, and the c-jun N-terminal kinase (JNK) pathways were detected with Western-blot analysis.We found that LBP appeared to exert these protective effects by inhibiting oxidative stress and the JNK/c-jun pathway and by transiently increasing production of insulin-like growth factor-1 (IGF-1).

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and the State Key Laboratory of Brain and Cognitive Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

ABSTRACT
Our group has shown that the polysaccharides extracted from Lycium barbarum (LBP) are neuroprotective for retinal ganglion cells (RGCs) in different animal models. Protecting RGCs from secondary degeneration is a promising direction for therapy in glaucoma management. The complete optic nerve transection (CONT) model can be used to study primary degeneration of RGCs, while the partial optic nerve transection (PONT) model can be used to study secondary degeneration of RGCs because primary degeneration of RGCs and secondary degeneration can be separated in location in the same retina in this model; in other situations, these types of degeneration can be difficult to distinguish. In order to examine which kind of degeneration LBP could delay, both CONT and PONT models were used in this study. Rats were fed with LBP or vehicle daily from 7 days before surgery until sacrifice at different time-points and the surviving numbers of RGCs were evaluated. The expression of several proteins related to inflammation, oxidative stress, and the c-jun N-terminal kinase (JNK) pathways were detected with Western-blot analysis. LBP did not delay primary degeneration of RGCs after either CONT or PONT, but it did delay secondary degeneration of RGCs after PONT. We found that LBP appeared to exert these protective effects by inhibiting oxidative stress and the JNK/c-jun pathway and by transiently increasing production of insulin-like growth factor-1 (IGF-1). This study suggests that LBP can delay secondary degeneration of RGCs and this effect may be linked to inhibition of oxidative stress and the JNK/c-jun pathway in the retina.

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Effects of LBP on RGC survival 1 week and 4 weeks after PONT.The RGCs were labeled with FG. (A) LBP did not increase the survival of RGCs either 1 week or 4 weeks after the PONT when the densities of surviving RGCs were produced from the whole retinas (NS: not significant). (B) When the retinas were divided into the superior and inferior halves, LBP did not delay the degeneration of RGCs 1 week after PONT. However, it reduced the degeneration of RGCs in the inferior retina (*P = 0.027) but not in the superior retina 4 weeks after the PONT. (F – H) The photographs of RGCs labeled by FG in both the superior and inferior retinas are about 1.5 mm away from the optic disc. In the superior retinas, the densities of RGCs were similar between the PBS and LBP groups. In the inferior retinas, the density of RGCs in the LBP group was higher than that in the PBS group. Microglia (white arrows) were easily distinguished from RGCs and not counted. (n = 7 and 4 in PBS and LBP groups 1 week after PONT. n = 9 and 10 in PBS and LBP groups 4 weeks after PONT.).
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pone-0068881-g005: Effects of LBP on RGC survival 1 week and 4 weeks after PONT.The RGCs were labeled with FG. (A) LBP did not increase the survival of RGCs either 1 week or 4 weeks after the PONT when the densities of surviving RGCs were produced from the whole retinas (NS: not significant). (B) When the retinas were divided into the superior and inferior halves, LBP did not delay the degeneration of RGCs 1 week after PONT. However, it reduced the degeneration of RGCs in the inferior retina (*P = 0.027) but not in the superior retina 4 weeks after the PONT. (F – H) The photographs of RGCs labeled by FG in both the superior and inferior retinas are about 1.5 mm away from the optic disc. In the superior retinas, the densities of RGCs were similar between the PBS and LBP groups. In the inferior retinas, the density of RGCs in the LBP group was higher than that in the PBS group. Microglia (white arrows) were easily distinguished from RGCs and not counted. (n = 7 and 4 in PBS and LBP groups 1 week after PONT. n = 9 and 10 in PBS and LBP groups 4 weeks after PONT.).

Mentions: The average densities of FG-labeled RGCs in the normal retinas were as follows: the whole retinas: 2088.1±64.4 RGCs/mm2; the normal superior retinas: 2046.5±92.4 RGCs/mm2; and the normal inferior retinas: 2144.4±89.8 RGCs/mm2. There was no difference between the superior and inferior retinas (Student’s t-test, P>0.05). The surviving RGC densities decreased significantly in the expected areas after both CONT and PONT in animals treated with PBS or LBP (Student’s t-test, P<0.001, Fig. 4 & Fig. 5). The surviving densities of RGCs after CONT from animals without treatment with PBS or LBP were as follows: 1510.7±65.6 in the superior retinas and 1402.6±74.7 in the inferior retinas 1 week after CONT; 234.2±19.8 in the superior retinas and 214.8±8.4 in the inferior retinas 2 weeks after CONT. There were no significant differences between the superior and inferior retinas at both time-points after CONT (Student’s t-test, P>0.05).


Lycium barbarum (wolfberry) reduces secondary degeneration and oxidative stress, and inhibits JNK pathway in retina after partial optic nerve transection.

Li H, Liang Y, Chiu K, Yuan Q, Lin B, Chang RC, So KF - PLoS ONE (2013)

Effects of LBP on RGC survival 1 week and 4 weeks after PONT.The RGCs were labeled with FG. (A) LBP did not increase the survival of RGCs either 1 week or 4 weeks after the PONT when the densities of surviving RGCs were produced from the whole retinas (NS: not significant). (B) When the retinas were divided into the superior and inferior halves, LBP did not delay the degeneration of RGCs 1 week after PONT. However, it reduced the degeneration of RGCs in the inferior retina (*P = 0.027) but not in the superior retina 4 weeks after the PONT. (F – H) The photographs of RGCs labeled by FG in both the superior and inferior retinas are about 1.5 mm away from the optic disc. In the superior retinas, the densities of RGCs were similar between the PBS and LBP groups. In the inferior retinas, the density of RGCs in the LBP group was higher than that in the PBS group. Microglia (white arrows) were easily distinguished from RGCs and not counted. (n = 7 and 4 in PBS and LBP groups 1 week after PONT. n = 9 and 10 in PBS and LBP groups 4 weeks after PONT.).
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Related In: Results  -  Collection

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pone-0068881-g005: Effects of LBP on RGC survival 1 week and 4 weeks after PONT.The RGCs were labeled with FG. (A) LBP did not increase the survival of RGCs either 1 week or 4 weeks after the PONT when the densities of surviving RGCs were produced from the whole retinas (NS: not significant). (B) When the retinas were divided into the superior and inferior halves, LBP did not delay the degeneration of RGCs 1 week after PONT. However, it reduced the degeneration of RGCs in the inferior retina (*P = 0.027) but not in the superior retina 4 weeks after the PONT. (F – H) The photographs of RGCs labeled by FG in both the superior and inferior retinas are about 1.5 mm away from the optic disc. In the superior retinas, the densities of RGCs were similar between the PBS and LBP groups. In the inferior retinas, the density of RGCs in the LBP group was higher than that in the PBS group. Microglia (white arrows) were easily distinguished from RGCs and not counted. (n = 7 and 4 in PBS and LBP groups 1 week after PONT. n = 9 and 10 in PBS and LBP groups 4 weeks after PONT.).
Mentions: The average densities of FG-labeled RGCs in the normal retinas were as follows: the whole retinas: 2088.1±64.4 RGCs/mm2; the normal superior retinas: 2046.5±92.4 RGCs/mm2; and the normal inferior retinas: 2144.4±89.8 RGCs/mm2. There was no difference between the superior and inferior retinas (Student’s t-test, P>0.05). The surviving RGC densities decreased significantly in the expected areas after both CONT and PONT in animals treated with PBS or LBP (Student’s t-test, P<0.001, Fig. 4 & Fig. 5). The surviving densities of RGCs after CONT from animals without treatment with PBS or LBP were as follows: 1510.7±65.6 in the superior retinas and 1402.6±74.7 in the inferior retinas 1 week after CONT; 234.2±19.8 in the superior retinas and 214.8±8.4 in the inferior retinas 2 weeks after CONT. There were no significant differences between the superior and inferior retinas at both time-points after CONT (Student’s t-test, P>0.05).

Bottom Line: Our group has shown that the polysaccharides extracted from Lycium barbarum (LBP) are neuroprotective for retinal ganglion cells (RGCs) in different animal models.The expression of several proteins related to inflammation, oxidative stress, and the c-jun N-terminal kinase (JNK) pathways were detected with Western-blot analysis.We found that LBP appeared to exert these protective effects by inhibiting oxidative stress and the JNK/c-jun pathway and by transiently increasing production of insulin-like growth factor-1 (IGF-1).

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and the State Key Laboratory of Brain and Cognitive Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

ABSTRACT
Our group has shown that the polysaccharides extracted from Lycium barbarum (LBP) are neuroprotective for retinal ganglion cells (RGCs) in different animal models. Protecting RGCs from secondary degeneration is a promising direction for therapy in glaucoma management. The complete optic nerve transection (CONT) model can be used to study primary degeneration of RGCs, while the partial optic nerve transection (PONT) model can be used to study secondary degeneration of RGCs because primary degeneration of RGCs and secondary degeneration can be separated in location in the same retina in this model; in other situations, these types of degeneration can be difficult to distinguish. In order to examine which kind of degeneration LBP could delay, both CONT and PONT models were used in this study. Rats were fed with LBP or vehicle daily from 7 days before surgery until sacrifice at different time-points and the surviving numbers of RGCs were evaluated. The expression of several proteins related to inflammation, oxidative stress, and the c-jun N-terminal kinase (JNK) pathways were detected with Western-blot analysis. LBP did not delay primary degeneration of RGCs after either CONT or PONT, but it did delay secondary degeneration of RGCs after PONT. We found that LBP appeared to exert these protective effects by inhibiting oxidative stress and the JNK/c-jun pathway and by transiently increasing production of insulin-like growth factor-1 (IGF-1). This study suggests that LBP can delay secondary degeneration of RGCs and this effect may be linked to inhibition of oxidative stress and the JNK/c-jun pathway in the retina.

Show MeSH
Related in: MedlinePlus