Chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats.

The nucleus accumbens (NAc), considered the hub of reward circuitry, is comprised of two medium spiny neuron (MSN) subtypes that are classified by their enrichment of dopamine 1 (D1) or 2 (D2) receptors. While reports indicate that alcohol increases excitatory neurotransmission exclusively on NAc D1-MSNs in male rats, it remains unknown how NAc MSNs control alcohol intake in either sex. Therefore, this study investigated how NAc MSNs mediate alcohol intake by using Drd1a-iCre and Drd2-iCre transgenic rats of both sexes. Intra-NAc infusions of Cre-inducible viral vectors containing stimulatory (hM3Dq) or inhibitory (hM4Di) designer receptors exclusively activated by designer drugs (DREADDs) were delivered after 4-weeks of alcohol intake, and clozapine-N-oxide (CNO) was administered to selectively manipulate NAc MSNs. Our results show that activation of NAc D1-MSNs increased alcohol intake 1-, 4-, and 24-h after the start of drinking while inhibition decreased it 1-h after the start of drinking, with no sex differences observed at any time point. Activation of NAc D2-MSNs had no impact on alcohol intake while inhibition increased alcohol intake in Drd2-iCre rats for 1-h in males and 4-h in females. These findings suggest opposing roles for how NAc D1- and D2-MSNs modulate alcohol intake in rats of both sexes.

Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats.

Clinical evidence suggests superior antidepressant response over time with a repeated, intermittent ketamine treatment regimen as compared to a single infusion. However, the club drug ketamine is commonly abused. Therefore, the abuse potential of repeated ketamine injections at low doses needs to be investigated. In this study, we investigated the abuse potential of repeated exposure to either 0, 2.5, or 5 mg/kg ketamine administered once weekly for seven weeks. Locomotor activity and conditioned place preference (CPP) were assayed to evaluate behavioral sensitization to the locomotor activating effects of ketamine and its rewarding properties, respectively. Our results show that while neither males nor females developed CPP, males treated with 5 mg/kg and females treated with either 2.5 or 5 mg/kg ketamine behaviorally sensitized. Furthermore, dendritic spine density was increased in the NAc of both males and females administered 5 mg/kg ketamine, an effect specific to the NAc shell (NAcSh) in males but to both the NAc core (NAcC) and NAcSh in females. Additionally, males administered 5 mg/kg ketamine displayed increased protein expression of ΔfosB, calcium calmodulin kinase II alpha (CaMKIIα), and brain-derived neurotrophic factor (BDNF), an effect not observed in females administered either dose of ketamine. However, males and females administered 5 mg/kg ketamine displayed increased protein expression of AMPA receptors (GluA1). Taken together, low-dose ketamine, when administered intermittently, induces behavioral sensitization at a lower dose in females than males, accompanied by an increase in spine density in the NAc and protein expression changes in pathways commonly implicated in addiction.

[Long-term follow-up 10 years after transpupillary thermotherapy (TTT) for small, posterior located malignant melanomas of the choroid]. / Langzeitverlauf 10 Jahre nach transpupillarer Thermotherapie (TTT) kleiner, posteriorer maligner Aderhautmelanome.

BACKGROUND: The aim of this study was to evaluate the long-term results of transpupillary thermotherapy (TTT) for small malignant choroidal melanomas. PATIENTS AND METHODS: In the time period 1/1998 to 10/1999 in a prospective non-randomised analysis 26 eyes with small malignant melanomas (located posterior to the equator with base ≤ 12 and thickness ≤ 4.5 mm) were primary treated with the TTT standard protocol (follow-up over a time span of at least 10 years). RESULTS: Thirteen women and thirteen men (mean age: 64 years) underwent TTT. The mean preoperative tumour thickness was 2.45 mm (0.8 - 4.5 mm). Ten years postoperatively tumour regression without recurrence after 1.4 treatment sessions (mean) was achieved in 16 / 26 eyes, primary regression followed by tumour regrowth in 6 / 26 eyes, and primary failure of tumour regression in 4 / 26 eyes. Two patients died on liver metastasis. Ocular complications (with preference in posterior tumours after multiple TTT sessions) were observed in 14 eyes: macular pucker in 8, macular oedema in 6, choroidal neovascularisation in 4 and posterior synechia with iris atrophy in one eye. CONCLUSIONS: Choroidal melanomas treated with TTT as a stand-alone procedure need a close monitoring since these tumours developed a significant rate of local recurrences and ocular side-effects in the long run.

[Idiopathic macular telangiectasia - follow-up with and without laser photocoagulation]. / Idiopathische makuläre Teleangiektasie (IMT) - Verlaufsbeobachtung mit und ohne Laserphotokoagulation.

PURPOSE: The aim of this study was to evaluate the effectiveness of laser photocoagulation for idiopathic macular telangiectasia (IMT) by using the revised and simplified classification of Yannuzzi 2006. PATIENTS AND METHODS: The Yannuzzi classification was used for a retrospective analysis of the medical records of all patients with idiopathic macular telangiectasia as diagnosed consecutively in the University Eye Clinic of Mainz in the time period from 1 / 02 to 12 / 06. Laser treatment was indicated only in those eyes which presented with a visual acuity below 10 / 20 (follow-up interval in median 37 months, minimum 13 months). RESULTS: 12 patients with unilateral macular telangiectasia (IMT type I) and 30 patients with bilateral macular telangiectasia (IMT type II) were recruited. In type I disease 9 / 12 patients were male with an average age of 41 years (range: 28 to 47). 10 / 12 eyes showed macular oedema. After focal laser photocoagulation in 6 / 10 eyes the macular oedema decreased in 4 / 6 eyes and visual acuity improved in 3 / 6 eyes. In type II disease 17 / 30 patients were male and the average age was 56 years (range: 45 to 63). All 60 eyes showed macular oedema. In 40 eyes, which did not receive a laser photocoagulation, the ocular findings did not change during the follow-up examinations. In 16 / 20 eyes the macular oedema has successfully been reduced by laser photocoagulation, however without significant visual improvement. In 2 of these 16 treated eyes the development of a subfoveal choroidal neovascularisation with central loss of vision was noted. CONCLUSIONS: In IMT type I laser photocoagulation was able to achieve a visual improvement. In IMT type II, however, a laser photocoagulation indication should be considered very carefully because in this group no visual improvement was reached and a secondary induction of subretinal neovascular membranes seems likely.

[Tumor regression in malignant choroidal melanomas after transpupillary thermotherapy (TTT) versus ruthenium brachytherapy and sandwich therapy - a comparative analysis]. / Tumorregression maligner Aderhautmelanome nach Transpupillarer Thermotherapie (TTT) versus Ruthenium-Brachytherapie und Sandwichtherapie - eine vergleichende Analyse.

PURPOSE: The aim of this study was to evaluate tumour regression in a large series of choroidal melanomas, which were treated with three different eye-sparing treatment modalities. PATIENTS AND METHODS: Retrospective review of the treatment results in all eyes with malignant choroidal melanoma, which were treated in the University Eye Clinic of Mainz consecutively in the time span 1.1992 to 12.2000 with transpupillary thermotherapy (TTT, standard protocol Oosterhuis JA 1995), ruthenium brachytherapy (RB, tumor apex dose 150 Gy) or sandwich therapy (ST). One-step ST was defined as TTT followed by RB with 100 Gy tumor apex dose within 48 hours. The treatment of residual prominences with TTT secondary to RB after different time spans was called two-step ST. Follow-up was 2 years. RESULTS: 131 eyes with malignant choroidal melanoma (mean tumour thickness: 4.5 mm) were treated with RB (66 eyes), TTT (26 eyes) or ST (39 eyes). Preservation of the globe was achieved in 109 eyes (81 %). Local tumour control was found in small melanomas (prominence up to 3 mm) in 89 %, in large tumors (prominence 8 mm and higher) in 50 %. In a subgroup of small posterior melanomas (n = 70 eyes, prominence up to 4.5 mm, located posterior to the equator) local tumour control was noted in 91 %. The time span to reach local tumour control (Kaplan-Meier estimates) was the shortest after TTT (median: 20 weeks), compared with RB (48 weeks) and one-step ST (29 weeks). CONCLUSIONS: In choroidal melanomas the chance of local tumour control and preservation of the globe decreases with increase of the tumour prominence. In small choroidal melanomas with posterior location local tumour control was achieved significantly faster after TTT than after RB.

[Eales' disease--10 years experience with a rare disease]. / Morbus Eales--10 Jahre Erfahrung mit einem seltenen Krankheitsbild.

BACKGROUND: Eales' disease is an uncommon vasoproliferative retinal disease affecting otherwise healthy young men. We report on our treatment results in a large patients group with long-term follow-up. PATIENTS AND METHODS: The treatment results in 50 eyes (35 patients) with Eales' disease, that were consecutively treated from May 1995 to August 2005, were analysed retrospectively. Recorded data included age, sex, race, association of systemic disease, medications, laboratory evaluation and the surgical treatment. Mean follow-up was 5.8 years (minimum: 3.2, maximum: 8.6 years). RESULTS: Systemic and laboratory evaluations detected a factor V Leiden mutation (4x), vestibuloauditory problems (1x) and migraine (1x). 10 eyes with peripheral non-perfusion, teleangiectasia and mild neovascularisations were treated by scatter laser photocoagulation alone. 18 eyes with advanced neovascularisations/vitreous haemorrhages received cryocoagulation too. 14 eyes with persistent or recurrent bleedings despite coagulation therapy and/or development of tractional retinal detachment were treated by vitrectomy. 5 of them received a silicone oil endotamponade. All eyes could be stabilised without further bleedings. Visual acuity increased in 25 eyes. Only 5 eyes showed a visual loss. The visual results (rate of improvements and the stages of visual acuity as well) were the best in those eyes that received vitrectomy. CONCLUSIONS: These results suggest that early retinal laser and cryocoagulation and - if necessary - vitrectomy in due time may led to a stabilised retina without further bleedings and visual improvement too. Coagulopathy could play a role in the pathogenesis of Eales' disease.

[Arteriovenous crossing sheathotomy in branch retinal vein occlusion]. / Arteriovenöse Dissektion (AVD) bei retinalen Venolenastverschlüssen.

BACKGROUND: The aim of this study is to report on arteriovenous sheathotomy in branch retinal vein occlusion (BRVO) with a long-term follow-up and examine the visual field effects of this surgical approach. PATIENTS AND METHODS: In a clinical trial 36 eyes with branch retinal vein occlusion (22 eyes with ischaemia, 14 eyes with chronic macular oedema) underwent surgical decompression accompanied by peeling of the membrana limitans interna after prior isovolemic haemodilution for 3 months had been unsuccessful. RESULTS: All eyes showed a significant reduction of macular oedema 3 months after surgery. During follow-up (median: 26.4 months) visual acuity increased in 24/36 eyes and was stabilised in 8/36 eyes. We observed haemorrhages at the dissection site (5x), vitreous haemorrhages (12x) and retinal holes at the vitreous base (2x). Goldmann perimetry revealed paracentral scotomas in 3 eyes, which had been treated by arteriovenous dissection relatively close to the optic disc. In 16/22 eyes with ischaemic thromboses the visual field was narrowed in the affected quadrant. CONCLUSIONS: The results of arteriovenous sheathotomy in BRVO are encouraging because we observed increase of visual acuity in 67% of the eyes in spite of an unsuccessful haemodilution during 3 months before. However, whether its benefits outweigh potential surgical complications as visual field defects remains to be determined.

[Central serous chorioretinopathy (CSC) and corticosteroids]. / Chorioretinopathia serosa centralis (CSC) und Kortikosteroide.

BACKGROUND: Corticosteroids are under suspicion of playing an important role in the development of central serous chorioretinopathy (CSC). PATIENTS AND METHODS: In a prospective study the course of CSC was evaluated in a consecutive series of 46 patients, who received the diagnosis of CSC in the period 4 / 2004 - 12 / 2005. Data analysis was focused on the complete medical and ocular history and the ocular course of this disease. RESULTS: 27 patients had been taking exogenous corticosteroids (oral, intravenous, inhalative, cutaneous and intraarticular) within 4 weeks before onset of symptoms. Additionally, one case with Cushing's disease and 2 pregnant women were included. These 30 / 46 patients with steroid association presented bilateral involvement in 21 cases (70 %) and angiographically more than one leakage point in 10 cases (33 %). In 16 / 46 patients without history of taking exogenous corticosteroids bilateral involvement was seen in 2 / 16 cases (13 %) and multiple leakages in only one case (6 %). CSC resolved spontaneously in 25 / 46 patients within 2 - 6 months. In 21 / 46 patients recurrences were documented either in the eye, which was primarily affected or in the other one. In this group of recurrent CSC all 8 patients were included who did not discontinue the use of systemic corticosteroids. CONCLUSIONS: These results strongly support the association of steroid use with CSC. Unter systemic treatment with corticosteroids bilateral involvement and multilocular leakages seem to be more likely than without use of steroids. All patients in need of corticosteroids by any systemic route of administration should be informed of the associated risk.

[Laser photocoagulation and photodynamic therapy (PDT) with verteporfin for retinal angiomatous proliferation (RAP) in age-related macular degeneration (AMD)]. / Laserfotokoagulation und photodynamische Therapie (PDT) zur Behandlung der retinalen angiomatösen Proliferation (RAP) bei feuchter altersabhängiger Makuladegeneration (AMD).

BACKGROUND: Retinal angiomatous proliferation (RAP) is a subtype of neovascular age-related macular degeneration (AMD) with particularly bad prognosis. Diverse treatment modalities are performed. PATIENTS AND METHODS: This is a retrospective review on the treatment results of 41 consecutive patients from 1/2003 to 12/2005 with RAP stage 1-3 (Yannuzzi classification), who were treated with laser photocoagulation, photodynamic therapy (PDT) and intravitreal injection of triamcinolone acetonide (IVT). Follow-up was 12 months minimally. RESULTS: In RAP stage I complete closure of the vascular lesion in 14 / 22 eyes was achieved by 1.2 +/- 0.5 sessions of laser photocoagulation (4 x combined with IVT) and in 3/14 eyes with photodynamic therapy (2 +/- 0.5 sessions). In RAP stage II closure of the lesion was achieved by 3.2 +/- 0.6 sessions of photodynamic therapy in 6/14 eyes (4 x combined with IVT). In RAP stage III closure of the lesion was achieved by 3.2 +/- 0.4 sessions of photodynamic therapy in 0 / 5 eyes (3 x combined with IVT). A rip of the retinal pigment epithelium was observed in 2/14 eyes of RAP stage II and 2/5 eyes of RAP stage III. Visual acuity improved in 9/17 eyes with occlusion of RAP stage I. Without closure of the vascular lesion all eyes got legally blind (visual acuity 1/50 or less). CONCLUSIONS: Early detection and subsequent direct treatment of RAP stage I in AMD is recommended. In advanced stages anatomical closure of the vascular complex is rarely achieved and the risk is improved for development of tears in the retinal pigment epithelium and getting legally blind.