slow-release-drug-delivery-through-elvax-40w-to-rat-retina

Slow-release Drug Delivery through Elvax 40W to the Rat Retina: Implications for the Treatment of Chronic Conditions

Diseases of the retina are difficult to treat as the retina lies deep within the eye. Invasive methods of drug delivery are often needed to treat these ...

UNIVERSITY OF L'AQUILA

We analysed the specific effects of IL-1beta immunoneutralization on the expression of IL-6 in different pure cultures of neurones and glia after both experimental subliminal hypoxia and recovery. Whereas the IL-1beta-deprivation signal induced a decrease in IL-6 expression and release of normoxic neurones, it provoked an increase in IL-6 protein in hypoxic neurones. Moreover, the direct correlation between IL-1beta and IL-6, observed in normal and recovering neuronal cultures, was reversed in hypoxic conditions. These reversals were not observed in glial cells, in which IL-1beta immunosuppression led to a decrease in IL-6 under all conditions considered. In conclusion, the IL-1beta modulates IL-6 in different ways according to the ambient physiological or pathological conditions, and also acts via different mechanisms, depending on the cellular phenotype.

Differential modulation of interleukin-6 expression by interleukin-1beta in neuronal and glial cultures.

To assess neurotrophic factor upregulation in the retina after damage to the optic nerve and relate that regulation to changes in photoreceptor stability and function.

Time course of neurotrophic factor upregulation and retinal protection against light-induced damage after optic nerve section.

The gradual restriction of initially multistratified retinal ganglion cell (RGC) dendrites into ON and OFF sublaminae of the inner plexiform layer (IPL) can be effectively blocked by treating the developing retina with 2-amino-4-phosphonobutyrate (APB), the metabotropic glutamate agonist, or by light deprivation. Previous studies have focused on the short-term consequences of such manipulations, so the long-term effects of arresting dendritic stratification on the structural development of RGCs are as yet unknown. In the present study, we have addressed this issue by performing a morphological analysis of alpha RGCs labeled by retrograde transport of horseradish peroxidase injected into the dorsal lateral geniculate nucleus of adult cats that received monocular injections of APB from postnatal (P) day 2 until P30. A large proportion of the alpha cells in the APB-treated eye (44%) were found to have multistratified dendrites that terminated in both the ON and OFF sublaminae of the IPL. The dendritic arborization pattern in the sublaminae of the IPL of these cells was asymmetric, showing a variety of forms. Immunolabeling of retinal cross-sections showed that mGLUR6 receptors appeared normal in density and location, while qualitative observation suggested an increase in the axonal arborization of rod bipolar cells. These findings indicate that long-term treatment of the neonatal retina with APB induces a long- lasting structural reorganization in retinal circuitry that most likely accounts for some of the previously described changes in the functional properties of RGCs.

Long-term treatment of the developing retina with the metabotropic glutamate agonist APB induces long-term changes in the stratification of retinal ganglion cell dendrites.

Calcium calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) was identified in crude extract and immunolabeled sections of rat retina. Both cAMP and cGMP PDE activities were stimulated by calcium-calmodulin (4.7-fold and 2.3-fold, respectively). To characterize PDE1 isoforms in retinal cells further, we used antibodies that specifically recognize PDE1 gene products. PDE1B antibody stained a band at molecular mass of 63 kDa whereas PDE1C antibody recognized two bands at 74- and 70-kDa molecular masses. Two PDE1A antibodies (against N-terminal and C-terminal peptides) detected a band at 79 kDa never described before. Immunohistochemical analysis showed a distribution of PDE1A in the outer retina with a bright fluorescence in the outer segments of photoreceptors. PDE1B is uniformly distributed across the retina. PDE1C is confined mainly to the inner retina, with a precise localization in the inner nuclear layer. Immunostaining with choline acetyltransferase antibody indicates localization in cholinergic amacrine cell. The present data provide evidence of expression of PDE1 isoforms in mammalian retina with a complementary distribution of PDE1A and PDE1C, suggesting different roles in retinal function.

Gene expression and protein localization of calmodulin-dependent phosphodiesterase in adult rat retina.

We investigated the rate of cell proliferation and death in the retina of the Monodelphis opossum during its postnatal development and the influence of early monocular enucleation on these processes. Our results show that in the opossum, as in other marsupials, the peak of the retinal cells divisions occurs postnatally and that generation of retinal cells continues till the time of eye opening (P34), except of the marginal rim, where it continued till P60. Ganglion and amacrine cells are generated between postnatal days (P) P4 and P9, while bipolar cells and photoreceptors are generated simultaneously between P14 and P25. The peak of ganglion cell death as detected by the TUNEL method occurs around P14-19 in the center of retina. The second peak of apoptosis appears in the inner nuclear layer (INL) at P19-25. Gliogenesis takes place between P25 and P34. We also found that monocular enucleation performed during the early period of retinal development (P0-P7) did not influence proliferation, developmental apoptosis or other developmental processes in the retina of the remaining eye.

Development and plasticity of the retina in the opossum Monodelphis domestica.

&#x6700;&#x8FD1;&#x7684;&#x6570;&#x636E;&#x63D0;&#x51FA;&#x8D28;&#x7591;&#x5149;&#x5177;&#x6709;&#x5F88;&#x5C11;&#x5BF9;&#x89C6;&#x7F51;&#x819C;&#x53D1;&#x80B2;&#x7684;&#x5F71;&#x54CD;&#x7684;&#x5047;&#x8BBE;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#xFF0C;&#x6211;&#x4EEC;&#x62A5;&#x544A;&#x9ED1;&#x6697;&#x9972;&#x517B;&#x6C38;&#x4E45;&#x66F4;&#x6539;&#x9009;&#x533A;&#x7684;&#x7A81;&#x89E6;&#x8F93;&#x5165;&#x7684;&#x8BC1;&#x636E;&#x3002;&#x51CF;&#x5C11;&#x81EA;&#x53D1;&#x7A81;&#x89E6;&#x540E;&#x7535;&#x6D41; (SPSCs) &#x9891;&#x7387;&#x4ECE;&#x51FA;&#x751F;&#x548C;&#x957F;&#x5927;&#x5728;&#x9ED1;&#x6697;&#x4E2D;&#x7684;&#x4E09;&#x4E2A;&#x6708;&#x7684;&#x5927;&#x9F20;&#x89C6;&#x7F51;&#x819C; Gc &#x4E2D;&#x53D1;&#x73B0;&#x3002;&#x8C37;&#x6C28;&#x9178;&#x62EE;&#x6297;&#x5242; (CNQX &#x548C; AP 5) &#x53EF;&#x9006;&#x51CF;&#x5C11; SPSCs &#x9891;&#x7387;&#x63A7;&#x5236;&#x548C;&#x9ED1;&#x6697;&#x9972;&#x517B; (DR) &#x89C6;&#x7F51;&#x819C;&#x8131;&#x79BB;&#x3002;GABA &#x62EE;&#x6297;&#x5242;&#x5316;&#x5B66; &#xFF08;PTX&#xFF09; &#x51CF;&#x5C11; SPSCs &#x9891;&#x7387;&#x63A7;&#x5236;&#x89C6;&#x7F51;&#x819C;&#xFF0C;&#x4F46;&#x589E;&#x52A0; SPSCs &#x9891;&#x7387;&#x5728;&#x535A;&#x58EB;&#xFF0C;&#x4E3B;&#x8981;&#x662F;&#x901A;&#x8FC7;&#x5BF9;&#x7535;&#x6D41;&#x5174;&#x594B;&#x6027;&#x7A81;&#x89E6;&#x524D;&#x884C;&#x52A8;&#x3002;&#x535A;&#x58EB;&#x52A8;&#x7269;&#x66DD;&#x5149;&#x6B63;&#x5E38;&#x5FAA;&#x73AF;&#x7684; 3 &#x4E2A;&#x6708;&#xFF0C;&#x5728; SPSCs &#x9891;&#x7387;&#x4ECD;&#x7136;&#x4F4E;&#x7136;&#x540E;&#x63A7;&#x5236;&#x5927;&#x9F20;&#x548C;&#x589E;&#x52A0;&#x4EE5;&#x4E0B; PTX&#xFF0C;&#x8FD9;&#x8868;&#x660E;&#x957F;&#x671F;&#x9ED1;&#x6697;&#x9972;&#x517B;&#x8BF1;&#x5BFC;&#x89C6;&#x7F51;&#x819C;&#x7684;&#x7535;&#x8DEF;&#x6C38;&#x4E45;&#x7684;&#x4FEE;&#x6539;&#x3002;&#x6211;&#x4EEC;&#x7684;&#x7814;&#x7A76;&#x7ED3;&#x679C;&#x5F3A;&#x70C8;&#x652F;&#x6301;&#x5149;&#x523A;&#x6FC0;&#x4F5C;&#x7528;&#x5728;&#x5EFA;&#x7ACB;&#x9009;&#x533A;&#x7684;&#x6B63;&#x5E38;&#x7A81;&#x89E6;&#x8F93;&#x5165;&#x7684;&#x60F3;&#x6CD5;&#x3002;

&#x957F;&#x671F;&#x9ED1;&#x6697;&#x9972;&#x517B;&#x8BF1;&#x5BFC;&#x89C6;&#x7F51;&#x819C;&#x7535;&#x8DEF;&#x4E2D;&#x7684;&#x6C38;&#x4E45;&#x91CD;&#x7EC4;&#x3002;

Recent data challenged the assumption that light has little effect on retina development. Here, we report evidence that dark rearing permanently changes the synaptic input to GCs. A reduced spontaneous postsynaptic currents (SPSCs) frequency was found in retinal GCs from rats born and raised in the dark for three months. Glutamate antagonists (CNQX and AP-5) reversibly reduced SPSCs frequency in control and dark-reared (DR) retinae. The GABA antagonist picrotoxin (PTX) reduced SPSCs frequency in control retinas, but increased SPSCs frequency in DR, mainly by presynaptic action on excitatory currents. In DR animals exposed to normal cyclic light for 3 months, SPSCs frequency remained lower then in control rats and increased following PTX, suggesting that long-term dark rearing induces permanent modifications of the retinal circuitry. Our results strongly support the idea that light stimulation plays a role in establishing normal synaptic input to GCs.

Long-term dark rearing induces permanent reorganization in retinal circuitry.

Des donn&eacute;es r&eacute;centes ont contest&eacute; l&#39;hypoth&egrave;se que la lumi&egrave;re a peu d&#39;effet sur le d&eacute;veloppement de la r&eacute;tine. Nous rapportons ici la preuve que l&#39;&eacute;levage sombre d&eacute;finitivement change l&#39;entr&eacute;e synaptique &agrave; la GCs. Une fr&eacute;quence r&eacute;duite spontan&eacute;e des courants postsynaptiques (SLES SSP) a &eacute;t&eacute; trouv&eacute;e dans la GCs r&eacute;tiniennes de rats n&eacute; et a grandi dans l&#39;obscurit&eacute; pendant trois mois. Antagonistes glutamate (CNQX et AP-5) r&eacute;duit r&eacute;versiblement fr&eacute;quence SLES SSP en contr&ocirc;le et &eacute;lev&eacute;s en noir les r&eacute;tines (DR). La picrotoxine antagoniste de GABA (PTX) r&eacute;duit la fr&eacute;quence de SLES SSP dans la r&eacute;tine de contr&ocirc;le, mais une augmentation de fr&eacute;quence de SLES SSP en RD, principalement par l&#39;action pr&eacute;synaptique sur courants excitateurs. DR animaux expos&eacute;s &agrave; la lumi&egrave;re de cyclique normale pendant 3 mois, fr&eacute;quence SLES SSP est rest&eacute; inf&eacute;rieur puis dans les rats t&eacute;moins et accru PTX suivant, ce qui sugg&egrave;re qu&#39;&eacute;levage sombre &agrave; long terme induit des modifications permanentes de la circuiterie r&eacute;tinienne. Nos r&eacute;sultats appuient fortement l&#39;id&eacute;e que la stimulation lumineuse joue un r&ocirc;le dans l&#39;&eacute;tablissement entr&eacute;e synaptique normale aux GCs.

&Eacute;levage sombre &agrave; long terme induit une r&eacute;organisation permanente dans les circuits de la r&eacute;tine.

Aktuelle Daten die Annahme, dass Licht kaum Auswirkungen auf die Entwicklung der Netzhaut hat in Frage gestellt. Hier berichten wir Beweise daf&uuml;r, dass dunkle Aufzucht dauerhaft zu GCs synaptische Eingabe &auml;ndert. Eine reduzierte spontane postsynaptisches Str&ouml;mungen (SPSCs)-Frequenz fand in retinalen GCs von Ratten geboren und aufgewachsen in der Dunkelheit f&uuml;r drei Monate. Glutamat-Antagonisten (CNQX und AP-5) reduziert umkehrbar SPSCs Frequenz Kontrolle und Dunkelheit aufgezogen (DR) Retinae. GABA Antagonist Picrotoxin (PTX) SPSCs Frequenz im Steuerelement Netzhaut verringert, sondern erh&ouml;ht SPSCs Frequenz in DR, haupts&auml;chlich durch pr&auml;synaptische Aktion auf exzitatorischen Str&ouml;mungen. In DR Tiere, zyklische Normallicht f&uuml;r 3 Monate ausgesetzt blieb SPSCs Frequenz niedriger dann Steuerelement Ratten und erh&ouml;hte folgende PTX, was darauf hindeutet, dass langfristige dunkle Aufzucht permanente &Auml;nderungen der Netzhaut Schaltung induziert. Unsere Ergebnisse unterst&uuml;tze die Idee, dass leichte Stimulierung eine Rolle spielt bei der Festlegung der normalen synaptische Eingabe f&uuml;r GCs.

Langfristige dunkle Aufzucht induziert permanente Reorganisation in retinalen Schaltkreise.

Dati recenti ha sfidato il presupposto che la luce ha poco effetto sullo sviluppo della retina. Riportiamo prove che dark allevamento permanentemente cambia l&#39;input sinaptico di GCs. Una frequenza ridotta correnti postsinaptiche spontanee (SPSCs) &egrave; stata trovata nella retina GCs da ratti nata e cresciuta nel buio per tre mesi. Antagonisti del glutammato (CNQX e AP-5) reversibilmente ridotta frequenza SPSCs in controllo e dark-allevati retinae (DR). Il picrotoxin antagonista GABA (PTX) ridotta frequenza SPSCs in retine di controllo, ma aumentata frequenza SPSCs in DR, principalmente dall&#39;azione presinaptica sulle correnti eccitatorie. DR animali esposti a luce normale ciclico per 3 mesi, frequenza SPSCs &egrave; rimasto quindi bassa nei ratti controllo e aumentato seguente PTX, suggerendo che allevamento scuro a lungo termine induce modificazioni permanenti della circuiteria retinica. I nostri risultati supportano fortemente l&#39;idea che la stimolazione luminosa gioca un ruolo nello stabilire normali input sinaptici di GCs.

Allevamento a lungo termine scuro induce la riorganizzazione permanente nella circuiteria retinica.

&#x6700;&#x8FD1;&#x306E;&#x30C7;&#x30FC;&#x30BF;&#x5149;&#x304C;&#x7DB2;&#x819C;&#x306E;&#x958B;&#x767A;&#x306B;&#x306F;&#x307B;&#x3068;&#x3093;&#x3069;&#x5F71;&#x97FF;&#x3092;&#x6301;&#x3063;&#x3066;&#x3044;&#x308B;&#x3053;&#x3068;&#x3092;&#x524D;&#x63D0;&#x306B;&#x6311;&#x6226;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;&#x6C38;&#x4E45;&#x306B;&#x6697;&#x3044;&#x98FC;&#x80B2; Gc &#x3078;&#x306E;&#x30B7;&#x30CA;&#x30D7;&#x30B9;&#x5165;&#x529B;&#x5909;&#x5316;&#x306E;&#x8A3C;&#x62E0;&#x3092;&#x5831;&#x544A;&#x3057;&#x307E;&#x3059;&#x3002;&#x524A;&#x6E1B;&#x81EA;&#x767A;&#x6027;&#x30B7;&#x30CA;&#x30D7;&#x30B9;&#x96FB;&#x6D41; (SPSCs) &#x5468;&#x6CE2;&#x6570;&#x7DB2;&#x819C;&#x306E; Gc &#x306B; 3 &#x30F6;&#x6708;&#x9593;&#x306E;&#x6697;&#x95C7;&#x306E;&#x4E2D;&#x3067;&#x751F;&#x307E;&#x308C;&#x80B2;&#x3063;&#x305F;&#x30E9;&#x30C3;&#x30C8;&#x304C;&#x898B;&#x3064;&#x304B;&#x308A;&#x307E;&#x305B;&#x3093;&#x3067;&#x3057;&#x305F;&#x3002;&#x30B0;&#x30EB;&#x30BF;&#x30DF;&#x30F3;&#x9178;&#x62EE;&#x6297;&#x85AC; (CNQX &#x3068; AP 5) &#x306F;&#x3001;&#x5143;&#x306B;&#x623B;&#x305B;&#x308B;&#x72B6;&#x614B; SPSCs &#x5468;&#x6CE2;&#x6570;&#x5236;&#x5FA1;&#x3068;&#x6697;&#x3044;&#x98FC;&#x80B2; (DR) &#x7DB2;&#x819C;&#x524A;&#x6E1B;&#x3002;GABA &#x62EE;&#x6297;&#x85AC;&#x30D4;&#x30AF;&#x30ED;&#x30C8;&#x30AD;&#x30B7;&#x30F3; (PTX) SPSCs &#x5468;&#x6CE2;&#x6570;&#x5236;&#x5FA1;&#x306E;&#x7DB2;&#x819C;&#x3067;&#x6E1B;&#x5C11;&#x3057;&#x305F;&#x304C;&#x3001;DR &#x3067; SPSCs &#x30B7;&#x30CA;&#x30D7;&#x30B9;&#x524D;&#x4F5C;&#x7528;&#x8208;&#x596E;&#x6027;&#x96FB;&#x6D41;&#x3092;&#x4E2D;&#x5FC3;&#x306B;&#x5897;&#x52A0;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;3 &#x30F6;&#x6708;&#x9593;&#x306B;&#x901A;&#x5E38;&#x306E;&#x74B0;&#x72B6;&#x306E;&#x5149;&#x306B;&#x3055;&#x3089;&#x3055;&#x535A;&#x58EB;&#x52D5;&#x7269;&#x3067;&#x306F;&#x3001;SPSCs &#x5468;&#x6CE2;&#x6570;&#x5236;&#x5FA1;&#x30E9;&#x30C3;&#x30C8;&#x3068;&#x9577;&#x671F;&#x7684;&#x306A;&#x6697;&#x3044;&#x98FC;&#x80B2;&#x7DB2;&#x819C;&#x56DE;&#x8DEF;&#x306E;&#x6C38;&#x4E45;&#x7684;&#x306A;&#x5909;&#x66F4;&#x3092;&#x8A98;&#x5C0E;&#x3059;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3001;&#x5897;&#x52A0;&#x306E;&#x4EE5;&#x4E0B; PTX &#x3067;&#x3001;&#x4F4E;&#x304F;&#x63A8;&#x79FB;&#x3002;&#x6211;&#x3005; &#x306E;&#x7D50;&#x679C;&#x306F;&#x5F37;&#x304F;&#x5149;&#x523A;&#x6FC0; Gc &#x3078;&#x306E;&#x901A;&#x5E38;&#x306E;&#x30B7;&#x30CA;&#x30D7;&#x30B9;&#x5165;&#x529B;&#x3092;&#x78BA;&#x7ACB;&#x3059;&#x308B;&#x5F79;&#x5272;&#x3092;&#x679C;&#x305F;&#x3057;&#x3066;&#x3044;&#x308B;&#x3068;&#x30A2;&#x30A4;&#x30C7;&#x30A2;&#x3092;&#x30B5;&#x30DD;&#x30FC;&#x30C8;&#x3057;&#x307E;&#x3059;&#x3002;

&#x9577;&#x671F;&#x7684;&#x306A;&#x6697;&#x3044;&#x98FC;&#x80B2;&#x7DB2;&#x819C;&#x56DE;&#x8DEF;&#x3067;&#x6052;&#x4E45;&#x7684;&#x306A;&#x518D;&#x7DE8;&#x3092;&#x8A98;&#x5C0E;&#x3057;&#x307E;&#x3059;&#x3002;

&#xCD5C;&#xADFC; &#xB370;&#xC774;&#xD130; &#xBE5B;&#xC740; &#xB9DD;&#xB9C9; &#xAC1C;&#xBC1C;&#xC5D0;&#xB294; &#xD6A8;&#xACFC;&#xAC00; &#xAC70;&#xC758; &#xAC00;&#xC815;&#xC5D0; &#xB3C4;&#xC804;. &#xC5EC;&#xAE30;, &#xC6B0;&#xB9AC;&#xAC00; &#xBCF4;&#xACE0; &#xC99D;&#xAC70; &#xC5B4;&#xB450;&#xC6B4; &#xC601;&#xAD6C;&#xC801;&#xC73C;&#xB85C; &#xC591;&#xC721; &#xD558;&#xB294; Gc &#xC2DC; &#xB0C5; &#xC2A4; &#xC785;&#xB825; &#xBCC0;&#xACBD;. &#xAC10;&#xC18C; &#xC790;&#xBC1C;&#xC801;&#xC778; postsynaptic &#xC804;&#xB958; (SPSCs) &#xC8FC;&#xD30C;&#xC218;&#xB294; &#xC950;&#xAC00; &#xD0DC;&#xC5B4;&#xB098; &#xACE0; &#xC5B4;&#xB460; &#xC18D;&#xC5D0;&#xC11C; &#xBC1C;&#xC0DD; &#xD558;&#xB294; 3 &#xAC1C;&#xC6D4;&#xC5D0;&#xC11C; &#xB9DD;&#xB9C9; Gc&#xC5D0;&#xC11C; &#xBC1C;&#xACAC; &#xB410;&#xB2E4;. &#xC870;&#xBBF8;&#xB8CC; &#xAE38; &#xD56D; &#xC81C; (CNQX &#xBC0F; AP-5)&#xB294; &#xC5ED; &#xC81C;&#xC5B4; &#xBC0F; &#xC5B4;&#xB450;&#xC6B4; reared (DR) retinae SPSCs &#xC8FC;&#xD30C;&#xC218; &#xAC10;&#xC18C;. GABA &#xC801;&#xC5D0; &#xAC8C; picrotoxin (PTX) &#xC81C;&#xC5B4; &#xB9DD;&#xB9C9;&#xC5D0;&#xC11C; SPSCs &#xC8FC;&#xD30C;&#xC218; &#xAC10;&#xC18C; &#xD558;&#xC9C0;&#xB9CC; presynaptic &#xC791;&#xC5C5; &#xD765;&#xBD84; &#xC131;&#xC758; &#xC804;&#xB958;&#xC5D0; &#xC758;&#xD574; &#xC8FC;&#xB85C; &#xBC15;&#xC0AC;&#xC5D0; SPSCs &#xC8FC;&#xD30C;&#xC218;&#xB97C; &#xC99D;&#xAC00; &#xD569;&#xB2C8;&#xB2E4;. &#xBC15;&#xC0AC; &#xB3D9;&#xBB3C; 3 &#xAC1C;&#xC6D4;&#xAC04; &#xC815;&#xC0C1; &#xC8FC;&#xAE30;&#xC801; &#xBE5B;&#xC5D0; &#xB178;&#xCD9C;, SPSCs &#xC8FC;&#xD30C;&#xC218; &#xC81C;&#xC5B4; &#xC950;&#xC640; &#xADF8;&#xC758; &#xB9DD;&#xB9C9; &#xD68C;&#xB85C; &#xC601;&#xAD6C; &#xC218;&#xC815; &#xC720;&#xB3C4; &#xC7A5;&#xAE30; &#xC5B4;&#xB450;&#xC6B4; &#xC591;&#xC721; &#xC81C;&#xC548; &#xC99D;&#xAC00; &#xB2E4;&#xC74C; PTX &#xB2E4;&#xC74C; &#xB0AE;&#xC740; &#xB0A8;&#xC544; &#xC788;&#xC5C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xC758; &#xACB0;&#xACFC; &#xAC15;&#xD558;&#xAC8C; &#xBE5B; &#xC790;&#xADF9;&#xC740; Gc&#xC5D0; &#xB300; &#xD55C; &#xC815;&#xC0C1;&#xC801;&#xC778; &#xC2DC; &#xB0C5; &#xC2A4; &#xC785;&#xB825; &#xC124;&#xC815; &#xC5ED;&#xD560; &#xC544;&#xC774;&#xB514;&#xC5B4;&#xB97C; &#xC9C0; &#xC6D0;&#xD558;&#xB294;.

&#xC7A5;&#xAE30; &#xC5B4;&#xB450;&#xC6B4; &#xC591;&#xC721; &#xB9DD;&#xB9C9; &#xD68C;&#xB85C;&#xC5D0; &#xC601;&#xAD6C; &#xC870;&#xC9C1; &#xAC1C;&#xD3B8;&#xC744; &#xC720;&#xB3C4;&#xD569;&#xB2C8;&#xB2E4;.

Datos recientes desafiaron la suposici&oacute;n de que la luz tiene poco efecto sobre el desarrollo de la retina. Presentamos evidencia que cr&iacute;a oscuro permanentemente cambia la entrada sin&aacute;ptica a GCs. Una frecuencia reducida corrientes postsin&aacute;pticos espont&aacute;nea (SPSCs) fue encontrada en GCs retinales de ratas naci&oacute; y se cri&oacute; en la oscuridad durante tres meses. Antagonistas de glutamato (CNQX y AP-5) reversible reducen la frecuencia de SPSCs en control y criados en oscuro (DR) retinas. El picrotoxin de antagonista GABA (PTX) reduce la frecuencia de SPSCs en retinas de control, pero aument&oacute; la frecuencia de SPSCs en Rep&uacute;blica Dominicana, principalmente por acci&oacute;n presin&aacute;ptica en corrientes excitatorias. En DR animales expuestos a luz c&iacute;clica normal durante 3 meses, frecuencia de SPSCs segu&iacute;a siendo entonces menor en las ratas de control y mayor PTX siguiente, lo que sugiere que a largo plazo oscuro cr&iacute;a induce modificaciones permanentes de la circuiter&iacute;a de la retina. Nuestros resultados apoyan fuertemente la idea de que luz estimulaci&oacute;n juega un papel en el establecimiento de entrada sin&aacute;ptica normal a GCs.

Cr&iacute;a de oscuro a largo plazo induce reorganizaci&oacute;n permanente en circuitos de la retiniano.

Calmodulin-dependent phosphodiesterase (PDE1) is a key enzyme in cyclic nucleotides metabolism. We studied its gene expression and protein localization during retinal development in chick embryos. Western blot and densitometric analysis demonstrated that the expression of the three isoforms changed during development. PDE1A was highly expressed at the early stages and decreased as development proceeded. PDE1B expression remained relatively low and constant over time. PDE1C showed a prominent increase (13-fold) between embryonic day (E) 7 and E13, followed by a moderate increase between E13 and postnatal day (P) 1. The presence of the enzyme in the different retinal locations was strongly modulated by development. PDE1A immunostaining was first detected at the ganglion cell level (E7), then in the outer retina (E15-E21). At P5, the immunostaining was confined in the optic fiber layer. Isoform C immunolocalization followed the same inner-outer pattern as isoform A. At 5 days posthatching (P5), the immunoreactivity was restricted, as well as for the isoform A, in the optic fiber layer. The isoform B immunolabelling was low and evenly distributed across the retina at all stages. The different developmental profiles of PDE1A, PDE1B, and PDE1C induced a temporal modulation in cyclic nucleotides concentration, suggesting specific roles of this enzyme in the morphofunctional development of retinal circuitry.

Gene expression and protein localization of calmodulin-dependent phosphodiesterase during ontogenesis of chick retina.

&#x82E5;&#x8981;&#x6D4B;&#x8BD5;&#x662F;&#x5426;&#x85CF;&#x7EA2;&#x82B1;&#x63D0;&#x53D6;&#x7269; (&#x85CF;&#x7EA2;&#x82B1;) &#x4F5C;&#x4E3A;&#x81B3;&#x98DF;&#x8865;&#x5145;&#x5242;&#x7ED9;&#x62B5;&#x6D88;&#x8FDE;&#x7EED;&#x66DD;&#x5149;&#x767D;&#x5316;&#x5927;&#x9F20;&#x89C6;&#x7F51;&#x819C;&#x7684;&#x5F71;&#x54CD;&#x3002;

&#x85CF;&#x7EA2;&#x82B1;&#x8865;&#x540E;&#x7834;&#x574F;&#x54FA;&#x4E73;&#x52A8;&#x7269;&#x7684;&#x89C6;&#x7F51;&#x819C;&#x4E2D;&#x7684;&#x5149;&#x7167;&#x5C04;&#x4FDD;&#x6301;&#x5F62;&#x6001;&#x548C;&#x529F;&#x80FD;&#x3002;

To test whether the saffron extract (Crocus sativus L.) given as a dietary supplement counteracts the effects of continuous light exposure in the albino rat retina.

Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina.

Pour tester si l&#39;extrait de safran (Crocus sativus L.) donn&eacute;e comme suppl&eacute;ment di&eacute;t&eacute;tique neutralise les effets de l&#39;exposition continue &agrave; la lumi&egrave;re dans la r&eacute;tine de rat albinos.

Suppl&eacute;ment au safran maintient la morphologie et la fonction apr&egrave;s exposition &agrave; endommager la lumi&egrave;re dans la r&eacute;tine chez les mammif&egrave;res.

Testen Sie, ob der Safran Extrakt (Crocus Sativus L.), die als Nahrungserg&auml;nzung gegeben die Auswirkungen der kontinuierlichen Lichtexposition in der Netzhaut des Albino-Ratte entgegenwirkt.

Safran Beilage beh&auml;lt Morphologie und Funktion nach Exposition gegen&uuml;ber Licht S&auml;ugetier-Netzhaut zu besch&auml;digen.

Per verificare se l&#39;Estratto di zafferano (Crocus sativus L.) dato come integratore alimentare contrasta gli effetti dell&#39;esposizione continua alla luce nella retina di ratto albino.

Supplemento zafferano mantiene morfologia e funzione dopo esposizione a danneggiare la luce nella retina dei mammiferi.

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Para probar si el extracto de azafr&aacute;n (Crocus sativus L.) como un suplemento diet&eacute;tico contrarresta los efectos de la exposici&oacute;n continua a la luz en la retina de ratas albinas.

Suplemento azafr&aacute;n mantiene la morfolog&iacute;a y funci&oacute;n despu&eacute;s de la exposici&oacute;n a da&ntilde;ar la luz en la retina mam&iacute;fero.

To evaluate the functional effect of short-term supplementation of saffron, a spice containing the antioxidant carotenoids crocin and crocetin, in early age-related macular degeneration (AMD).

Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration.

This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague-Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution.

Bright light exposure reduces TH-positive dopamine neurons: implications of light pollution in Parkinson's disease epidemiology.

The Ikaros gene encodes a Krüppel-like zinc-finger transcription factor involved in hematopoiesis regulation. Ikaros has been established as one of the most clinically relevant tumor suppressors in several hematological malignancies. In fact, expression of dominant negative Ikaros isoforms is associated with adult B-cell acute lymphoblastic leukemia, myelodysplastic syndrome, acute myeloid leukemia and adult and juvenile chronic myeloid leukemia. Here, we report the isolation of a novel, non-canonical Ikaros splice variant, called Ikaros 11 (Ik11). Ik11 is structurally related to known dominant negative Ikaros isoforms, due to the lack of a functional DNA-binding domain. Interestingly, Ik11 is the first Ikaros splice variant missing the transcriptional activation domain. Indeed, we demonstrated that Ik11 works as a dominant negative protein, being able to dimerize with Ikaros DNA-binding isoforms and inhibit their functions, at least in part by retaining them in the cytoplasm. Notably, we demonstrated that Ik11 is the first dominant negative Ikaros isoform to be aberrantly expressed in B-cell lymphoproliferative disorders, such as chronic lymphocytic leukemia. Aberrant expression of Ik11 interferes with both proliferation and apoptotic pathways, providing a mechanism for Ik11 involvement in tumor pathogenesis. Thus, Ik11 could represent a novel marker for B-cell lymphoproliferative disorders.

A novel, non-canonical splice variant of the Ikaros gene is aberrantly expressed in B-cell lymphoproliferative disorders.

To determine whether the functional effects of oral supplementation with Saffron, a natural compound that proved to be neuroprotective in early age-related macular degeneration, are influenced by complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk genotypes.

Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report.

Age-related macular degeneration (AMD) is a retinal neurodegenerative disease whose development and progression are the results of a complex interaction between genetic and environmental risk factors. Both oxidative stress and chronic inflammation play a significant role in the pathogenesis of AMD. Experimental studies in rats with light-induced photoreceptors degeneration demonstrated that saffron may protect photoreceptor from retinal stress, preserving both morphology and function and probably acting as a regulator of programmed cell death, in addition to its antioxidant and anti-inflammatory properties. Recently, a randomized clinical trial showed that in patients with early AMD, dietary supplementation with saffron was able to improve significantly the retinal flicker sensitivity suggesting neuroprotective effect of the compound. Here, we examine the progress of saffron dietary supplementation both in animal model and AMD patients, and discuss the potential and safety for using dietary saffron to treat retinal degeneration.

Article	Year
Differential modulation of interleukin-6 expression by interleukin-1beta in neuronal and glial cultures. European cytokine network\| PubMed ID: 12957790	2003
Time course of neurotrophic factor upregulation and retinal protection against light-induced damage after optic nerve section. Investigative ophthalmology & visual science\| PubMed ID: 15851578	2005
Long-term treatment of the developing retina with the metabotropic glutamate agonist APB induces long-term changes in the stratification of retinal ganglion cell dendrites. Developmental neuroscience\| PubMed ID: 15855769	2004
Gene expression and protein localization of calmodulin-dependent phosphodiesterase in adult rat retina. Journal of neuroscience research\| PubMed ID: 16881052	2006
Development and plasticity of the retina in the opossum Monodelphis domestica. Acta neurobiologiae experimentalis\| PubMed ID: 17133949	2006
Long-term dark rearing induces permanent reorganization in retinal circuitry. Biochemical and biophysical research communications\| PubMed ID: 17999915	2008
Gene expression and protein localization of calmodulin-dependent phosphodiesterase during ontogenesis of chick retina. Journal of neuroscience research\| PubMed ID: 18041092	2008
Saffron supplement maintains morphology and function after exposure to damaging light in mammalian retina. Investigative ophthalmology & visual science\| PubMed ID: 18326756	2008
Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration. Investigative ophthalmology & visual science\| PubMed ID: 20688744	2010
Bright light exposure reduces TH-positive dopamine neurons: implications of light pollution in Parkinson's disease epidemiology. Scientific reports\| PubMed ID: 23462874	2013
A novel, non-canonical splice variant of the Ikaros gene is aberrantly expressed in B-cell lymphoproliferative disorders. PloS one\| PubMed ID: 23874502	2013
Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report. Journal of translational medicine\| PubMed ID: 24067115	2013
Saffron and retina: Neuroprotection and pharmacokinetics. Visual neuroscience\| PubMed ID: 24819927	2014

Rita Maccarone

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